1. cell

CELL

The human organism presents about 200 different cell types, all derived from the zygote, the single cell formed by fertilization of an oocyte with a spermatozoon.

During their specialization process, called cell differentiation, the cells synthesize specific proteins, change their shape, and become very efficient in specialized functions.

The body's cells can experience both normal and pathological conditions and the same cell type can exhibit different characteristics and behaviors in different regions and circumstances

CELLULAR FUNCTIONS IN SOME SPECIALIZED

CELLS.

The cell is composed of two basic parts:

Cytoplasm and

Nucleus.

Individual cytoplasmic components are usually not clearly distinguishable in common hematoxylin-and-eosin–stained preparations.

The nucleus, appears intensely stained dark blue or black.

The cytoplasm is composed of a fluid component, or cytosol, which containes metabolically active structures, the organelles, which can be membranous (such as mitochondria) or non-membranous protein complexes (such as ribosomes and proteasomes).

Membranous organelle

Non-Membranous organelle

Rough & Smooth Endoplasmic reticulum

Ribosomes

Mitochondria Centrioles

Golgi apparatus Microtubules

Peroxisomes Inclusions

Lysosomes Cilia - Flagella

Vacuoles & vesicles Microvilli

PLASMA MEMBRANE

The outermost component of the cell, separating the cytoplasm from its extracellular environment, is the Plasma membrane or Plasmalemma.

All eukaryotic cells are enveloped by a limiting membrane composed of phospholipids, cholesterol, proteins, and chains of oligosaccharides covalently linked to phospholipid and protein molecules.

Membranes range from 7.5 to 10 nm in thickness and visible only in the electron microscope.

With electron microscopy, the plasmalemma and, all other organellar membranes appears a trilaminar structure after fixation in osmium tetroxide.

Because all membranes have this appearance, the 3-layered structure was designated the unit membrane.

 Membrane phospholipids, such as phosphatidylcholine (lecithin), consist of two non-polar (hydrophobic or water-repelling) long-chain fatty acids linked to a charged polar (hydrophilic or water-attracting) head group.

Membrane phospholipids are most stable when organized into a double layer (bilayer) with their hydrophobic fatty acid chains directed toward the middle away from water and their hydrophilic polar heads directed outward to contact water on both sides.

Cholesterol molecules insert among the close packed the phospholipid

fatty acids nearly a 1:1 ratio , restricting their movement, and thus modulate the fluidity and movement of all membrane components.

The lipid composition of each half of the bilayer is different.

In red blood cells phosphatidylcholine and sphingomyelin are more abundant in the outer half of the membrane, whereas phosphatidylserine and phosphatidylethanolamine are more concentrated in the inner half.

Some of the lipids, known as glycolipids, possess oligosaccharide chains that extend outward from the surface of the cell membrane and thus contribute to the lipid asymmetry. 

Proteins, are major molecular constituent of membranes, can be divided into two groups.

Integral proteins :o Incorporated within the lipid bilayer. o Some integral proteins span the membrane one or more times,

from one side to the other, they are called one-pass or multipass transmembrane proteins.

Peripheral proteins : exhibit a looser association with one of the two

membrane surfaces.

With freeze-fracture electron microscope studies of membranes show that many integral proteins are only partially embedded in the lipid bilayer and protrude from either the outer or inner surface.

Transmembrane proteins are large enough to extend across the two lipid layers and may protrude from both membrane surfaces.

The carbohydrate moieties of the glycoproteins and glycolipids project from the external surface of the plasma membrane; they are important components of specific molecules called receptors that participate in important interactions such as cell adhesion, recognition, and response to protein hormones.

As with lipids, the distribution of membrane proteins is different in the two surfaces of the cell membranes. Therefore, all membranes in the cell are asymmetric.

Integration of the proteins within the lipid bilayer is mainly the result of hydrophobic interactions between the lipids and nonpolar amino acids present on the outer region of the proteins.

Some membrane proteins are not bound rigidly in place and are able to move within the plane of the cell membrane.

unlike lipids, most membrane proteins are restricted in their lateral diffusion by attachment to cytoskeletal components.

In most epithelial cells, tight junctions also restrict lateral diffusion of unattached transmembrane proteins and outer layer lipids to specific membrane domains.

The mosaic disposition of membrane proteins and the fluid nature of the lipid bilayer and led to the well-established fluid mosaic model for membrane structure.

Functions of plasmalemma :

A selective barrier.

To keep constant the ion content of cytoplasm.

Specific recognition and regulatory functions.

GLYCOCALYX

With the EM the external surface of the cell shows a fuzzy carbohydrate-rich region called the glycocalyx.

This layer is made of carbohydrate chains linked to membrane proteins and lipids and of cell-secreted glycoproteins and proteoglycans.

The glycocalyx has a role in cell recognition and attachment to other cells and to extracellular molecules.

Some ions, such as Na+, K+, and Ca2+, cross the cell membrane by passing through integral membrane proteins.

This can involve passive diffusion through ion channels or active transport via ion pumps using energy from the breakdown of adenosine triphosphate (ATP).

ENDOCYTOSIS

Bulk uptake of material also occurs across the plasma membrane in a general process called endocytosis, which involves folding and fusion of this membrane to form vesicles which enclose the material transported.

Cells show three general types of endocytosis.

1. Phagocytosis

2. Fluid-phase Endocytosis

3.Receptor-mediated Endocytosis

  Phagocytosis :

o Certain white blood cells, such as macrophages and neutrophils, are specialized for engulfing and removing particulate matter such as bacteria, protozoa, dead cells, and unneeded extracellular constituents.

o When a bacterium becomes bound to the surface of a neutrophil, cytoplasmic processes of the cell are extended and ultimately surround the bacterium.

o The membranes of these processes meet and fuse, enclosing the bacterium in an intracellular vacuole, a phagosome.

PHAGOCYTOSIS

Fluid-phase Endocytosis :

In fluid-phase pinocytosis , smaller invaginations of the cell membrane form and entrap extracellular fluid and anything it has in solution.

Pinocytotic vesicles (about 80 nm in diameter) pinch off inwardly from the cell surface.

In most cells such vesicles usually fuse with lysosomes.

PINOCYTOSIS

Receptor-mediated Endocytosis : Receptors for many substances, such as low-density

lipoproteins and protein hormones, are integral proteins of the cell membrane.

Binding of the ligand (a molecule with high affinity for a receptor) to its receptor causes widely dispersed receptors to aggregate in special membrane regions called coated pits.

The electron-dense coating on the cytoplasmic surface of the membrane is composed of several polypeptides, the major one being Clathrin.

In a developing coated pit clathrin molecules, forming that region of cell membrane into a cage-like invagination that is pinched off into the cytoplasm, forming a coated vesicle carrying the ligand and its receptor.  

RECEPTOR-MEDIATED ENDOCYTOSIS

In endocytotic processes, the vesicles or vacuoles produced quickly enter and fuse with the endosomal compartment, a dynamic system of membranous vesicles and tubules located in the cytoplasm near the cell surface (early endosomes) or deeper in the cytoplasm (late endosomes).

The clathrin molecules separated from the coated vesicles recycle to the cell membrane to participate in the formation of new coated pits.

The membrane of endosomes contains ATP-driven H+ pumps that acidify their interior.

While phagosomes and pinocytotic vesicles soon fuse with lysosomes, molecules penetrating the endosomal compartment after receptor-mediated endocytosis may take more than one pathway.

The acidic pH of early endosomes causes many ligands to uncouple from their receptors, after which the two molecules are sorted into separate vesicles.

The receptors may be returned to the cell membrane to be reused. The ligands typically are transferred to late endosomes. Some ligands are returned to the extracellular milieu with their

receptors and both are used again. Late endosomes most commonly fuse with lysosomes for

degradation of their contents.

EXOCYTOSIS

In exocytosis a membrane-limited cytoplasmic vesicle fuses with the plasma membrane, resulting in the release of its contents into the extracellular space without compromising the integrity of the plasma membrane.

Often exocytosis of stored products from epithelial cells occurs specifically at the apical domains of cells, such as in the exocrine pancreas and the salivary glands.

The fusion of membranes during exocytosis is a highly regulated process involving interactions between several specific membrane proteins.

Exocytosis is triggered in many cells by transient increase in cytosolic Ca2+.

During endocytosis, portions of the cell membrane become endocytotic vesicles; during exocytosis, the membrane is returned to the cell surface.

This process of membrane movement and recycling is called membrane trafficking.

Trafficking and sorting of membrane components occur continuously in most cells and are not only crucial for cell maintenance but also physiologically important in processes such as reducing blood lipid levels.

SIGNAL RECEPTION AND TRANSDUCTION

Cells in a multicellular organism need to communicate with one another to regulate their development into tissues, to control their growth and division, and to coordinate their functions.

Soluble extracellular signaling molecules bind receptor proteins only found on their target cells.

Each cell type in the body contains a distinctive set of receptor proteins that enable it to respond to a complementary set of signaling molecules in a specific, programmed way.

Signaling can take different routes:

Endocrine signaling: the signal molecules (called hormones) are carried in the blood to target

cells throughout the body.

Paracrine signaling : the chemical mediators are rapidly metabolized so that they act only on

local cells very close to the source.         

Synaptic signaling : a special kind of paracrine interaction, neurotransmitters act only on

adjacent cells through special contact areas called synapses.

Autocrine signaling : signals bind receptors on the same cell type that produced the messenger

molecule.    

Hydrophilic signaling molecules :

including most hormones, local chemical mediators (paracrine signals), and neurotransmitters activate receptor proteins on the surface of target cells.

These receptors, often transmembrane proteins, relay information to a series of intracellular intermediaries that ultimately pass the signal (first messenger) to its final destination in either the cytoplasm or the nucleus in a process called Signal transduction.

One of the intermediary proteins, the G proteins, binds guanine nucleotides and acts on other membrane-bound intermediaries called effectors which propagate the signal further into the cell.

Effector proteins are usually ion channels or enzymes that generate large quantities of small second messenger molecules, such as 1,2-diacyglycerol (DAG), cyclic adenosine monophosphate (cAMP), and inositol 1,4,5-triphosphate (IP3).

The ions or second messengers diffuse through the cytoplasm, amplifying the first signal and triggering a cascade of molecular reactions that lead to changes in gene expression or cell behavior.

MEDICAL APPLICATION

Several diseases have been caused by defective receptors. Pseudohypoparathyroidism and a type of Dwarfism are

caused by nonfunctioning parathyroid and growth hormone receptors.

In these two conditions the glands produce the respective hormones, but the target cells do not respond because they lack normal receptors.

Hydrophobic signaling molecules :

such as small steroid and thyroid hormones, bind reversibly to carrier proteins in the plasma for transport through the body.

Such hormones are lipophilic and once released from their carrier proteins, they diffuse directly through the plasma membrane lipid bilayer of the target cell and bind to specific intracellular receptor proteins.

With many steroid hormones, receptor binding activates that protein, enabling the complex to move into the nucleus and bind with high affinity to specific DNA sequences.

This generally increases the level of transcription from specific genes.

NUCLEUS

The nucleus contains a blueprint for all cell structures and activities encoded in the DNA of the chromosomes .

Nucleus is the site of deoxyribonucleic acid (DNA) replication and transcription of DNA into precursor ribonucleic acid (RNA)molecules.

It contains all of the enzymes required for replication and repair of newly synthesized DNA, as well as for transcription and processing of precursor RNA molecules.

It is enclosed by the nuclear envelope and contains the nuclear lamina, nucleolus, and chromatin

Nuclear envelope :

The nuclear envelope is a double membrane containing pores that are approximately 90 nm in diameter.

The outer nuclear membrane is continuous with the endoplasmic reticulum.

Nuclear Lamina :

The nuclear lamina is a latticelike network of proteins that include lamins.

Lamins attach chromatin to the inner membrane of the nuclear envelope and participate in the breakdown and reformation of the nuclear envelope during the cell cycle.

Phosphorylation of the lamins, (by lamin kinase) during prophase of mitosis initiates nuclear disassembly into small vesicles.

Functions:

Maintenance of nuclear shape

Spatial organization of nuclear pores within nuclear membrane

Regulation of transcription

Anchoring of interphase heterochromatin

DNA replication.

Nuclear Lamina

Lamina

bio.winona.msus.edu/.../ Lec-note/16-new.htm

Nucleolus :

The nucleolus is responsible for ribosomal RNA (rRNA) synthesis and ribosome assembly.

It contains three morphologically distinct zones:

• Granular zone—found at the periphery; contains ribosomal precursor particles in various stages of assembly.

• Fibrillar zone—centrally located; contains ribonuclear protein fibrils.

• Fibrillar center—contains DNA that is not being transcribed.

Nucleolus :

The nucleolus is responsible for ribosomal RNA (rRNA) synthesis and ribosome assembly.

It contains three morphologically distinct zones:

• Granular zone—found at the periphery; contains ribosomal precursor particles in various stages of assembly.

• Fibrillar zone—centrally located; contains ribonuclear protein fibrils.

• Fibrillar center—contains DNA that is not being transcribed.

Chromatin :Chromatin is a complex of DNA, histone proteins, and nonhistone

proteins.

• DNA—a double-stranded helical molecule that carries the genetic information of the cell.

It exists in three conformations: B DNA, Z DNA, and A DNA.

• Histone proteins—positively charged proteins enriched with lysine and arginine residues.

They are important in forming two types of structures in chromatin: nucleosomes and solenoid fibers.

The nucleosomes are the basic repeating units of the chromatin fiber, having a diameter of approximately 10 nm.

• Nonhistone proteins—include enzymes involved in nuclear functions such as replication, transcription, DNA repair, and regulation of chromatin function.

They are acidic or neutral proteins.

Chromatin

6 nucleosomes become coiled around an axis, forming a solenoid.

Nucleosome, Solenoid model of chromatin, and chromosome

Nucleosome

Forms of Chromatin :

• Heterochromatin :

highly condensed and transcriptionally inactive. In a typical eukaryotic cell, approximately 10% of the

chromatin is heterochromatin.

• Euchromatin :

a more extended form of DNA, which is potentially transcriptionally active.

In a typical cell, euchromatin accounts for approximate 90%of the total chromatin, although only about 10% is being actively transcribed.

CYTOPLASM

RIBOSOMES Ribosomes are composed of rRNA and protein. They

consist of large (60S) and small (40S) subunits. Ribosomes are assembled in the nucleus and transported

to the cytoplasm through the nuclear pores. The large ribosomal subunits are synthesized in the

nucleolus, whereas the small subunits are synthesized in the nucleus.

Polysomes : Ribosomes often form polysomes, which consist of a

single messenger RNA (mRNA) that is being translated by several ribosomes at the same time.

The ribosomes move on the mRNA from the 5' end towards 3' end.

The two ribosomal subunits associate on the mRNA, with the small subunit binding first

Forms of Ribosomes :

Ribosomes exist in two forms:

• Free polysomes : are the site of synthesis for proteins destined for the nucleus, peroxisomes, or mitochondria.

• Membrane-associated polysomes : are the site of synthesis of secretory proteins, membrane proteins, and lysosomal enzymes.

ENDOPLASMIC RETICULUM

The endoplasmic reticulum exists in two forms, rough endoplasmic reticulum (RER) and smooth endoplasmic reticulum (SER).

Rough Endoplasmic Reticulum : RER is a single, lipid bilayer continuous with the outer

nuclear membrane. It is organized into stacks of large flattened sacs called

cisternae that are studded with ribosomes on the cytoplasmic side.

RER snthesize poteins that are destined for the Golgi apparatus, secretion, the plasma membrane, and lysosomes.

RER is very prominent in cells that are specialized in the synthesis of proteins destined for secretion

(eg : pancreatic acinar cells).

ENDOPLASMIC RETICULUM

SMOOTH ENDOPLASMIC RETICULUM

Smooth Endoplasmic Reticulum :

SER is a network of membranous sacs, vesicles, and tubules continuous with the RER, but lacking ribosomes.

SER contains enzymes involved in the synthesis of phospholipids, triglycerides, and sterols

Functions of SER :

o Detoxification Reactions : Hydroxylation. Conjugation.o Glycogen Degradation and Gluconeogenesiso Reactions in Lipid Metabolismo Sequestration and Release of Calcium Ions

GOLGI APPARATUS

GOLGI APPARATUS

The Golgi apparatus consists of disc-shaped smooth cisternae that are assembled in stacks (dictyosomes), and associated with numerous small membrane-bound vesicles.

The Golgi apparatus has two distinct faces:

• The cis (forming) face is associated with the RER.

• The trans (maturing) face is often oriented toward the plasma membrane.

Important in glycosylation, phosphorylation, sulfation, etc.

Takes part in synthesis, concentration & storage of

secretory products.

Functions of the Golgi Apparatus :

Proteins and Lipids The Golgi apparatus is the site of post trauslational

modification and sorting of newly synthesized proteins and lipids.

Glycoproteins Further modification of the carbohydrate moiety of

glycoproteins produces complex and hybrid oligosaccharide chains.

This determines which proteins remain in the Golgi apparatus or leave the Golgi apparatus to become secretory proteins, lysosomal proteins, or part of the plasma membrane.

Two diseases are caused by a breakdown in this process, I-cell disease and hyperproinsulinemia

MEDICAL APPLICATION

Hyperprolnsulinemia :

Hyperprolnsulinemia is characterized by elevated levels of proinsulin in the serum resulting from the failure of a peptidase to cleave proinsulin to insulin and C-peptide in the golgi apparatus.

I-Cell Disease :

Phosphorylation of mannose in glycoproteins targets proteins to lysosomes.

Phosphate is added in a two-step sequence of reactions that are catalyzed by N-acetylglucosamine-phosphotransferase and N-acetylglucosaminidases.

A deficiency in N-acetylglucosamine-phosphotransferase results In I-cell dieease .

LYSOSOMES

Lysosomes are spherical membrane-enclosed organelles that are contain enzymes required for intracellular digestion.

Lysosomes consist of two forms :

•Primary lysosomes have not yet acquired the materials to be digested.

They are formed by budding from the trans side of the Golgi apparatus.

•Secondary lysosomes are formed by the fusion of the primary lysosome with the substrate to be degraded and have contents that are in various stages of degradation

Lysosomes contain approximately 60 hydrolytic enzymes.

• All lysosomal enzymes are acid hvdrolases, with optimal activity at a pH of approximately 5.0.

The synthesis of the lysosomal hydrolases occurs in RER.

All hydrolasea are transferred to the Golgi apparatus where they are modified and packaged into lysosomes.

MEDICAL APPLICATION

Glycogen-Storage Disease Type II (Pompe Disease) : an autosomal recessive disorder that results from the deficiency of

acid alpha-glucosidase, a lysosomal hydrolase , is required for the degradation of a small percentage (1-3%) of cellular glycogen.

Because the main pathway for glycogen degradation is not deficient in glycogen-storage disease type II disease, energy production is not impaired, and hypoglycemia does not occur.

However, the deficiency of this enzymatic activity results in the accumulation of structurally normal glycogen in lysosomes and cytoplasm in affected individuals.

Excessive glycogen storage within lysosomes may interrupt normal functioning of other organelles and leads to cellular injury. In turn, this leads to enlargement and dysfunction of the entire organ involved (eg, cardiomyopathy).

RESIDUAL BODIES

•Lysosomes containing indigestible compounds are called residual bodies. •The indigestible compounds are usually exocytosed.

•The unreleased indigestible compounds in long-living cells appear as lipofuscins or aging pigments.

RESIDUAL BODIES IN LUNG CELLS

AUTOPHAGOSOMES

Primary Liposomes fuse

with membrane-bound

organelles or a portion

of cytoplasm to form

autophagosomes.

Autolysis occurs when

lysosomes rupture and

destroy the cell itself.

PEROXISOMES

Peroxisomes are a heterogeneous group of small, spherical organelles with a single membrane.

Functions:

Synthesis and degradation of hydrogen peroxide. Oxidation of very long chain fatty acids (> C24). Phospholipid exchange. Bile acid synthesis.

PEROXISOMES (MICROBODIES )

MEDICAL APPLICATION

Peroxisome Deficiency :

Several genetic diseases are associated with the impairment or absence of peroxisomes.

These patients fail to oxidize very long chain fatty acids and accumulate bile acid precursors.

The four most common disorders are:

• Zellweger (cerebrohepatorenal) syndrome

• Neonatal adrenoleukodystrophy

• Infantile Refsum disease

• Hyperlipopecolaternia

MITOCHONDRIA

MITOCHONDRIA

Mitochondria have two membranes , They synthesize adenosine triphosphate (ATP), contain their own double-stranded circular DNA, and make some of their own proteins.

Mitochondria have several compartments :

Outer Membrane The outer membrane is smooth, continuous,

and highly permeable. It contains an abundance of porins, an integral

membrane protein that forms channels in the outer membrane through which molecules of

less than 10 kD can pass.

Inner Membrane The inner membrane is inpermiable to most small ions (Na,

K*, H*) and small molecules (ATP, adenosine diphosphate, pyruvate).

The impermeability is likely related to the high content of the lipid cardiolipin.

The inner membrane has numerous infoldings, called cristae.

The cristae greatly increase the total surface area. They contain, enzymes for electron transport and oxidative phosphorylation.

The number of mitochondria arid the number of cristae per mitochondrion are proportional to the metabolic activity of the cells in which they reside.

Mitochondria

Two types of cristae: tubular-like and plate-like. Most cells contain mitochondria with plate-like cristae. Steroidsecreting cells (eg. Adrenal, gonadal cells) have tubular cristae

Mitochondria

Internal membrane contains enzymes for:

•electron transport system •oxidative phophorylationsystems

Oxidative Phosphorylation

Intermembrane Compartment : The intermembrane compartment is the space between

the inner and outermembranes. It contains enzymes that use ATP to phosphorylate other

nucleotides (creatine phosphokinase and adenylate kinase).

Matrix : The matrix is enclosed by the inner membrane and

contains:

Dehydrogenases : oxidize many of the substrates in the cell (pyruvate, amino acids, fatty acids), generating reduced nicotinamide adenine dinucleotide (NADH) and reduced flavin adenine dinucleotide (FADH,) for use by the electron transport chain and energy generation.

Mitochondria

Matrix contains enzymes for:

•Citric acid cycle for generationof ATP

•Dehydrogenases

Citric acid cycle

A double-stranded circular DNA genome—encodes a few of the mitochondrial proteins.

Mitochondrial DNA is always inherited from the mother, resulting in transmission of diseases of enery metabolism.

RNA, proteins and ribosomes—although there is some protein synthesis, most mitochondrial proteins are synthesized in the cytoplasm and are transferred into the mitochondria.

Intramitochondrial granule : contain calcium and magnesium. Their function is not known, but it is believed that they may represent a storage site for Calcium.

CYTOSKELETON

CYTOSKELETON

Network-like structure.

Provides the shape of the cell.

Participates in transportation of large molecules.

Can even move the entire cell

Cytoskeleton

Cells contain 3 categories of cytoskeletal elements

•Microfilaments (actin filaments)

•Intermediate filaments

•Microtubules

MICROTUBULES

Small hollow cylindrical unbranched tubules 25 nm in diameter with a 5nm thick wall.

Made of 13 tubulin protofilaments arranged side by side around a central core

Microtubules play a role in:

Chromosomal movement during meiosis and mitosis. Microtubule assembly is an important event in spindle

formation. Intracellular vesicle and organelle transport. Two

specific microtubuledependent ATPases, kinesin and dynein, are involved in generating the force that drives transport, with the rnicrotubular structure playing a more passive role in intracellular transport.

Ciliary and flagellar movement.

The heterodimer, the subunit

of microtubule,is composed of

α and β tubulin molecules.

It is organized into a spiral

during polymerization.

A total of 13 units are

present in one complete

turn of the spiral.

Microtubule

•Microtubule formation generally occurs more rapidly at one end of existing microtubules.• This end is called the plus (+) end, and the other end as the minus (-) end.

Transportation in microtubules is under control of special proteins called motor proteins (dynein and kinesin)

Kinesins:Motor protein responsible for moving vesicles and organelles away from cell center.

Dyneins:Responsible for movement on microtubule towards the cell center.

•Microtubule formation directed by microtubule organizing center. •Is under control of concentration of Ca 2+ & microtubule associated proteins (MAPs).

Microtubule

Microtubule organizing center

CHEDIAK - HIGASHI SYNDROME :

Defect in microtubule polymerization .

is an autosomal recessive immunodeficiency disorder characterized by abnormal intracellular protein transport.

Leads to delayed fusion of phagosomes with lysosomes

in leukocytes

Centrioles

A pair of cylindrical structures with their long axis perpendicular to each other.

Each is composed of 9 sets of

Microtubule triplets arranged in the

fashion of pinwheel.

CENTRIOLE

Functions of centrioles

Non-dividing cells:•Polymerization of long single microtubules that radiate throughout the cytoplasm

•Maintain cell shape

•Transportation of substances

Dividing cells:•Form mitotic spindles

Microfilaments

Actin filaments

Microfilaments

•Made up of polymers of the protein actin

•Actin present as globular form (G-actin) & filamentous form (F-actin).

•F-actin polymerizes forming helically entwined actin chains

•These chains easily dissociate &reassemble with changes in levels of Ca 2+ & cAMP change.

Microfilaments (Ankyrin)

Ankyrin anchorsactin-filamentsto the integralproteins of The plasma membrane

Integral protein

Ankyrin

Most microfilament-related Movement depends upon the interaction between actin and another protein – myosin

Actin-myosin interaction results in contraction or relaxation of muscle fibers.

Microfilaments (Myosin)

Microfilaments (Dystrophin)

Transmembrane protein that links:

Short actin filaments beneath plasma membrane

Extends across plasma membrane to bind to extracellular matrix

Dystrophin

Dystrophin

Microfilaments (Dystrophin & muscular dystrophy)

Genetic disorder due to mutation in gene coding for the Actin binding protein, dystrophin

Intermediate filaments

• Vimentin : in cells of mesenchymal origin; may contribute to position the nucleus in the cell; polymerize with other intermediate filaments

• Desmin : Z-disks of skeletal muscle cells, where they link actin filaments of adjacent sarcomeres, ensure uniform tension distribution

• Glial fibrillary acid protein : characteristic of the cytoplasm of glial cells (astrocytes)

• Neurofilaments : formed by three distinct proteins, they are present in the cytoplasm of neurons

• Keratins : in cells of the skin for resistance to friction & cell to cell adhesion

Intermediate filaments(Epidermolysis bullosa)

Genetic disorder due to mutation in gene coding for keratin.

Results in increased skin fragility & blister formation

cell membrane

Apical cell membrane: Regulation of nutrient and water intakeRegulated secretionProtection

Lateral cell membrane:Desmosomes or macula adherensCell contact and adhesionCell communication

Basal cell membrane:Cell substratum contactGeneration of ion gradientsType IV collagen ,glycoproteins

Junctional complexes of epithelial cells.

Junctional complexes:

• Barrier to fluid flow• Maintain apical/basolateral polarity in cells• Maintain cell shape• Cell to cell communication

Tight Junction (Zonula Occludens) :

The tight junction is formed by the fusion of opposed cell membranes. These ridges of fusion present as "sealing strands" seen in freeze-fracture replicas.

It extends completely around the apical cell borders to

seal the underlying intercellular clefts from contact with the outside environment.

It constitutes the anatomic component of many barriers in the body.

Zonula Adherens :

A zonula adherens (adherent junction) often lies basal to the zonula occludens.

It is a bandlike junction that serves in the attachment of adjacent epithelial cells.

(Macula Adherens) Desmsomes

Desmosome The desmosome (macula adherens) is formed by the

juxtaposition of two disk-shaped plaques contained within the cytoplasm of each adjacent cell

Intermediate filaments (tonofilaments) radiate away from the plaques.

These intermediate filaments are anchored by desmoplakins (plaques) that also bind to transmembrane linker proteins, linking adjacent cells.

Cadherin molecules form actual anchor by attaching to cytoplasmic plaque, extending through the membrane and binding strongly to cadherins coming through the membrane of adjacent cell.

Desmosomes are most common in lining membranes, are subject to wear and tear, and are considered spot welds that hold cells together.

GAP JUNCTIONS

Gap Junction : The gap junction is an area of communication between

adjacent cells that allows the passage of very small particles an ions across a small intercellular gap within the junction .

The gap junction consists of a hexagonal lattice of tubular protein subunits called connexons, which form hydrophilic channels connecting the cytoplasm of adjacent cells.

This permits the direct passage of ions and small molecules between cells to conduct electrical impulses.

BASEMENT MEMBRANE

The basement membrane is a sheet like structure that underlies virtually all epithelia.

It consists of Basal lamina—composed of type IV collagen,

glycoproteins (e.g.,laminin), and proteoglycans

(e.g., heparan sulfate). Reticular lamina—composed of delicate reticular fibers.

Hemidesmsomes

Points of contact between cell and the extracellular matrix.Intermediate filaments of the cytoskeleton are inserted into disc shaped electron dense attachment plaque on the inside of the cell membrane.

APICAL (FREE) SURFACE SPECIALIZATIONS

Microvilli : Microvilli are apical cell surface evaginations of cell

membranes that function to increase the cell surface area available for absorption.

A thick glycocalyx coat covers them. The core of each microvillus contains actin microfilaments.

It is anchored in the apical cell cytoplasm to the terminal web, which itself is anchored to the zonula adherens of the cell membrane.

Cilia : Cilia are apical cell surface projections of cell membrane

that contain microtubules They are inserted on centriole-like basal bodies present

below the membrane surface at the apical pole. Cilia contain two central microtubules surrounded by a

circle of nine peripheral microtubule doublets. The peripheral doublets are fused so that they share a

common tubule wall and form two subtubules, A and B. Adjacent doublets are connected to one another by nexin

links

Cilia

Movement of Cilia : A pair of Dynein arms is attached to each A subtubule.

The arms bind to ATP and rearrange themselves so that a binding site for the B subtubule in the tip of the arm is exposed.

The B tubule interacts with the binding site, causing the arm to snap back and movement to occur.

Each cycle of a single dynein arm slides adjacent doublets 10 nm past each other.

Cilia move back and forth to propel fluid and particles in one direction.

They are important in clearing mucous from the respiratory tract.

FLAGELLA

TYPES OF CELLS

1. Labile

2. Stable

3. Permanent

Labile cells :

are dividing all the time--always in the cell cycle.

Examples : cells in the Digestive tract,

Skin,

Respiratory tract,

and Stem cells in the bone marrow producing blood cells.

STABLE CELLS

Also known as quiescent cells

Normally they have a low level of replication

Can rapidly divide in response to stimuli

Cells that make up glandular organs is an example of stable cells

pancreatic cells

During those periods of high mitotic rate, they are vulnerable to mutation & consequent malignancies

PERMANENT CELLS

Unable to divide

Can increase in size and accelerate their function

Examples:

Brain

Renal corpuscles

Cardiac muscle

Very resistant to neoplasia!cardiac muscle