Cell Biology Lecture 6
Dec 19, 2015
Cell BiologyLecture 6
Nucleus
Structural components (molecular structure and function of each component)
1. Nuclear envelope
2. Nucleoskeleton
3. Nuclear pores
4. Chromatin
5. Nucleolus
6. Sub-nuclear bodies: Cajal bodies, PIKA, PML bodies, Paraspeckles, Speckles
Functions:
1. Gene expression regulation
2. Nuclear transport
3. Cell compartmentalization
4. Processing of pre-mRNA
Disease and dynamics:
OUTLINE
The NUCLEAR COMPARTMENTnucleus or nuculeus, meaning kernel
• Largest most obvious double membrane-bound cellular organelle in animals.
• Dense, roughly spherical
• In mammalian cells, the average diameter 6 micrometers (μm), 10% of total cell volume.
• Nucleoplasm, similar in composition to the cytosol
maintains the integrity of genes
controls the cellular activities by regulating gene expression
production of other cell components
cell's growth
reproduction
A nucleated and multinucleated cells
RBC
Skeletal muscle, filamentous fungi
Functions as “The control center of the cell “
The Structural components
Nuclear envelope
The nuclear envelope consists of
1. two nuclear membranes, arranged
parallel to one another
2. an underlying nuclear lamina
3. nuclear pore complexes
completely encloses the nucleus, separates the cell's genetic material from the
surrounding cytoplasm, serving as a barrier to prevent macromolecules from diffusing
freely between the nucleoplasm and the cytoplasm.
The outer nuclear membrane is continuous with the
membrane of the rough endoplasmic reticulum (RER), and is
similarly studded with ribosomes. the outer nuclear membrane
contains various proteins found in far higher concentrations
than the endoplasmic reticulum
The Inner membrane
The inner nuclear membrane encloses the nucleoplasm, and is
covered by the nuclear lamina, It is connected to the outer
membrane by nuclear pores which penetrate the membranes.
the inner nuclear membrane carries unique proteins that are
specific to the nucleus.
The space between the membranes is called the perinuclear space (It is
typically about 20–40 nm wide) and is continuous with the RER lumen.
Nuclear envelope
Nucleoskeleton: NUCLEAR LAMINA
Underlying the inner nuclear membrane, a fibrous network within the nucleus that
1. adds mechanical support, much like the cytoskeleton, which supports the cell as
a whole
2. involved in chromatin function and gene expression.
• The nuclear lamina is composed of one or more related proteins called lamins.
• Most mammalian cells contain four different lamins, designated A, B1, B2, and C.
• All the lamins are 60- to 80-kilodalton (kd) fibrous proteins that are related to the
intermediate filament proteins of the cytoskeleton .
The association of lamins with the inner nuclear membrane is facilitated by the post
translational addition of lipid—in particular, prenylation of C-terminal cysteine residues
In addition, the lamins bind to inner nuclear membrane proteins, which may help organize the
lamin filaments into a meshwork and mediate their attachment to the membrane.
lamins associate with each other to form
filaments
1. Two lamins form a dimer in which the α-
helical regions of two polypeptide chains
are wound around each other in a structure
called a coiled coil.
2. Two of these dimer structures then join
side by side, to form a tetramer called a
protofilament
3. Eight of these protofilaments form a lateral
arrangement that is twisted to form a
ropelike filament.
Structural organization
Medical implication:
Mutations in lamin genes leading to defects in filament assembly are known as
laminopathies. The most notable laminopathy is the family of diseases known as
progeria, which causes the appearance of premature aging in its sufferers. The
exact mechanism by which the associated biochemical changes give rise to the
aged phenotype is not well understood.
NUCLEAR PORE COMPLEX
• Because the nuclear membrane is impermeable to large molecules, nuclear pores are required that
regulate nuclear transport of molecules across the envelope.
•The nucleus of a typical mammalian cell will have about 3000 to 4000 pores throughout its envelope.
• Pore complex is composed of 50 to 100 different proteins collectively referred to as nucleoporins.
•125 mega Daltons in molecular weight , about 30 times the size of a ribosome
•The pores are 100 nm in total diameter; however, the gap through which molecules freely diffuse is only
about 9 nm wide, due to the presence of regulatory systems within the center of the pore.
• Movement of large molecules such as proteins and RNA through the pores is required for both gene
expression and the maintenance of chromosomes. They must be actively transported by carrier proteins
while allowing free movement of small molecules and ions.
WHY:
This size allows the not-free passage of small water-soluble molecules while preventing
larger molecules, such as nucleic acids and larger proteins, from in-appropriately entering
or exiting the nucleus. These large molecules must be actively transported into the
nucleus instead.
•A ring-shaped structure at a position
where the inner and outer membranes
fuse.
•Attached to the ring is nuclear basket
that extends into the nucleoplasm, and a
series of filamentous extensions that
reach into the cytoplasm. Both structures
serve to mediate binding to nuclear
transport proteins.
•The central channel is approximately 40
nm in diameter, which is wide enough to
accommodate the largest particles able
to cross the nuclear envelope. It contains
a structure called the central transporter,
through which the active transport of
macromolecules is thought to occur.
STRUCTURE
1. Ran (RAs-related Nuclear protein) …interacting with karyopherins and changing their ability to bind or
release cargo molecules.
2. Cargo proteins containing a nuclear localization signal (NLS) are bound by importins and transported into
the nucleus.
3. Inside the nucleus, RanGTP binds to importin and releases the import cargo.
4. Cargo that needs to get out of the nucleus (carrying NES) into the cytoplasm binds to exportin in a ternary
complex with RanGTP. Upon hydrolysis of RanGTP to RanGDP outside the nucleus, the complex
dissociates and export cargo is released.
Transport Mechanism
importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo
1. The nuclear envelope separates the contents of the nucleus from the cytoplasm
2. provides the structural framework of the nucleus.
3. acting as barriers that prevent the free passage of molecules between the nucleus
and the cytoplasm, maintain the nucleus as a distinct biochemical compartment.
4. Phospholipid bilayers, which are permeable only to small nonpolar molecules ,
Other molecules are unable to diffuse through the phospholipid bilayer.
5. Nuclear pore complex sole channel, allow the regulated exchange of molecules
between the nucleus and cytoplasm.
6. The selective traffic of proteins and RNAs through the nuclear pore complexes not
only establishes the internal composition of the nucleus, but also plays a critical role
in regulating eukaryotic gene expression.
FUNCTIONS OF NUCLEAR ENVELOPE
Assignment 4 classes of ATP powered pumpsWrite in your words Paraphrase