Chapter 9

Chapter 9

Cell Communication

I. Overview of Cell Communication

• Ligand: molecule used as a signal, acts like a messenger

• Receptor: molecule signal binds to, receives message

• Signal Transduction: turn signal info into a cell response

1. Types of Signaling Defined by Distance

A. Direct contact: molecules sent to receptors on adjacent cells or through gap junctions.

B. Paracrine signaling: short-lived molecules that are released in the extracellular fluid to travel to neighboring cells.

C. Endocrine signaling: molecules or hormones that last a long time and travel long distances through the circulatory system.

D. Synaptic signaling: short-lived molecules called neurotransmitters travel across a synapse to send a message from one neuron to the next.

2. Signal transduction leads to cellular responses• Once the hormone glucagon binds to a

receptor, cells break down glycogen to become glucose and enzymes are produced to make glucose.

• The hormone epinephrine or adrenaline binds to different types of cells producing different cell responses.

• http://www.pennhealth.com/health_info/animationplayer/epinephrine.html

3. Phosphorylation controls protein function

• Phosphorylation: addition of a phosphate group

• Dephosphorylation: removal of a phosphate group

• Phosphorylation of proteins helps them to send info to generate a cellular response.

A. Protein kinase: enzyme that adds phosphate group from ATP to a protein activating it.

B. Phosphatase: enzymes that remove phosphate group from protein deactivating it.

II. Receptor Types

• When the ligand and receptor bind, the shape of the receptor changes which activates it.

1. Intracellular receptors: bind to signals or ligands inside of cell.

2. Cell surface or membrane receptors: transmembrane proteins. There are 3 classes.

A. Channel-linked receptor: gated ion channels w/ central pore, signaled to open or close by ligands.

B. Enzymatic Receptor: Protein kinase, enzyme activated by ligand.

C. G Protein-coupled receptors: a ligand binds to the receptor, this actives the G protein which then activates the effector protein or enzyme. G proteins act as assistants.

3. Membrane receptors activate second messengers.

• Second messengers: small molecules or ions that bind to proteins. Examples:

- cyclic adenosine monphosphate (cAMP)

- calcium ions

9.3 Intracellular Receptors

• These are LIPID-SOLUBLE or SMALL MOLECULES that can enter cell or even the nucleus.

1. Steroid Hormones:

- Bind to and activates ligand-receptor complex in cytoplasm. This complex enters nucleus hence we call it nuclear receptor.

- Examples: testosterone and estrogen

A. Steroid hormone receptor domains:i. hormone-binding domainii. DNA-binding domainiii. Domain that works with coactivators to control gene transcription

http://highered.mcgraw-hill.com/sites/0072943696/student_view0/chapter10/animation__mechanism_of_steroid_hormone_action__quiz_2_.html

B. Coactivator: molecules that help receptor complex bind to DNA to begin transcription. Coactivators cause different types of cells to respond differently to the same ligand.

C. Other intracellular receptors

i. Acetylcholine binds to receptors which activate the intracellular messenger Ca2+. This messenger activates the production of nitric oxide.

ii. Guanylyl cyclase binds to ligand nitric oxide (NO). This enzyme makes cyclic guanosine monophosphate or cGMP. cGMP is an intracellular messenger that relaxes smooth muscle.

9.4 Signal Transduction through Receptor Kinase

• Activate proteins through phosphorylation.

• Receptor tyrosine kinase (RTK) control the cell cycle, cell migration, cell metabolism, and cell proliferation.

1. RTK activated by autophosphorylation

A. 3 parts: transmembrane domain that holds RTK in membrane, ligand binding domain outside of cell, and kinase domain inside.

B. When ligand binds to receptors, 2 associate (dimerization) and phosphorylate each other (add phosphosphate groups)

2. Phosphotyrosine binds to proteins initiating a response.A. Insulin response protein becomes

phosphorylated by RTK and begins activation of a series of proteins which leads to the conversion of glucose to glycogen.

3. Protein kinase cascades can amplify a signalA. Series of protein kinases phosphorylate

each other. In each step, kinase acts on many substrates amplifying or increasing the signal. In the final step, MAP kinase is phosphorylated. This is called a phosphorylation or kinase cascade.

B. Mitogen-Activated Protein (MAP) Kinase: activate cell division.

4. Scaffold proteins organize kinase cascades

A. Complexes that holds kinase in each level of the cascade so that the substrate is next to each enzyme.

B. This can be a disadvantage as enzymes cannot freely interact reducing the cascade effect.

5. Ras

A. Ras is a GTP-binding protein or G-protein. It links the activation of RTK to a MAP kinase cascade. Ras can be quickly inactivated or turned off and thus acts like a control for cell division.

6. RTK are inactivated by interalization

A. RTK can be inactivated or shut off by dephosphorylation (removal of phosphate groups) or internalization (RTK is moved into a vesicle by endocytosis and broken down).

V. (9.5) Signal Transduction through G Protein - Coupled Receptors (GPCR)1. G protein links receptor with effector protein.

A. G proteins turned on by GTP.

B. Heterotrimeric: 3 parts to G protein in GPCR – G G G. When activated:

i. G + GTP can activate an effector protein

ii. G can activate an effector protein.

2. Effector proteins produce multiple second messengers

• ***Effector proteins – adenylyl cyclase and phopholipase C produce second messengers cyclic AMP and inositol phosphates

• http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__second_messenger__camp.html

A. Cyclic AMP or cAMP

• Second messenger in animal cells

• Ligand binds to GPCR activates adenylyl cyclase produces cAMP activates protein kinase A (PKA) phosphorylates protein for cell response.

http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html

WHY IS THIS IMPORTANT?(Example from book do not write)

• CHOLERA

• When the toxins from the bacteria vibrio cholera bind to a GPCR, it keeps GPCR in the “on” mode. Masses of cAMP are produced causing Cl- to leave cells. Water also leaves and this leads to dehydration and diarrhea.

B. Inositol phosphates• Common second messenger – inositol

phospholipid.

• The enzyme phopholipase C will convert PIP2 to secondary messengers DAG and IP3.

• phophatidylinositol-4,5-biphosphate (PIP2) inositol-1,4,5-triphosphate (IP3) diacylglycerol DAG

http://entochem.tamu.edu/G-Protein/index.html

C. Calcium Ca2+

• Ca2+ act as second messengers

• When receptors on the endoplasmic reticulum bind to IP3, calcium ions are released.

4 Ca2+ can bind to protein calmodulin to active proteins and effect cellular responses.

3. Different receptors can produce the same second messengers.

4. Receptor subtypes can lead to different effects in different cells.

5. G protein-coupled receptors and receptor tyrosine kinase can activate the same pathways.

VI. Cell-to-Cell Interactions

• Cells all have different identities due to expression of specific genes.

• Since they are specialized, they must find ways to communicate with each other.

1. Surface proteins give cells identity

A. Glycolipids: markers, IDs

B. MHC (major histocompatibility complex): cell recognition of “self” and “nonself” by immune system.

2. Cell connections mediate cell-to-cell adhesion

A. Cell Junctions: permanent connections between cells.

i. Tight junctions

• Connect plasma membrane of adjacent cells.

• Prevent small molecules from leaking b/t cells.

• Materials pass through junctions from one cell to the next.

• Separates plasma membrane into sections.

ii. Anchoring junctions/desmosomes

• Proteins called cadherins are linked to intermediate filaments of cytoskeleton.

• Cadherins on adjacent cells are linked.

• This binds and holds cells together.

• Adheren junctions connect the actin filaments or extracellular matrix of neighboring cells using integrins.

iii. Communicating junctions

• Allows small molecules or electric signals to pass from one cell to next.

• Gap junctions (animal cells): proteins called connexons form channels that open or close.

• Plasmodesmata (plant cells): occur at holes in cell walls, lined with cell membrane, and contain a tubule that connects the endoplasmic reticulum of two cells, and creates a path for signals.

• http://www.celanphy.science.ru.nl/Bruce%20web/Flash%20Movies.htm