1. CHAPTER 9 LECTURE SLIDES
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2. Cell Communication
Chapter 9

3. Overview Communication between cells requires
Ligand – signaling molecule
Receptor protein – molecule to which the receptor binds
Interaction of these two components initiates the process of signal transduction, which converts the information in the signal into a cellular response

5. There are four basic mechanisms for cellular communication
Direct contact
Paracrine signaling
Endocrine signaling
Synaptic signaling
Some cells send signals to themselves (autocrine signaling)

6. Direct contact
Molecules on the surface of one cell are recognized by receptors on the adjacent cell
Important in early development
Gap junctions

7. Paracrine signaling
Signal released from a cell has an effect on neighboring cells
Important in early development
Coordinates clusters of neighboring cells
Signaling between immune cells

8. Endocrine signaling
Hormones released from a cell travel through circulatory system to affect other cells throughout the body
Both animals and plants use this mechanism extensively

9. Synaptic signaling
Animals
Nerve cells release the signal (neurotransmitter) which binds to receptors on nearby cells
Association of neuron and target cell is a chemical synapse

10. Signal transduction
Events within the cell that occur in response to a signal
When a ligand binds to a receptor protein, the cell has a response
Different cell types can respond differently to the same signal
Epinephrine example

11. Phosphorylation Addition of phosphate group
A cell’s response to a signal often involves activating or inactivating proteins
Phosphorylation is a common way to change the activity of a protein
Protein kinase – an enzyme that adds a phosphate to a protein
Phosphatase – an enzyme that removes a phosphate from a protein

13. Receptor Types Receptors can be defined by their location
Intracellular receptor – located within the cell
Cell surface receptor or membrane receptor – located on the plasma membrane to bind a ligand outside the cell
Transmembrane protein in contact with both the cytoplasm and the extracellular environment

14. 3 subclasses of membrane receptors
Chemically gated ion channels – channel-linked receptors that open to let a specific ion pass in response to a ligand
Enzymatic receptors – receptor is an enzyme that is activated by the ligand
Almost all are protein kinases
G protein-coupled receptor – a G-protein (bound to GTP) assists in transmitting the signal from receptor to enzyme (effector)

16. Intracellular Receptors
Steroid hormones
Common nonpolar, lipid-soluble structure
Can cross the plasma membrane to a steroid receptor
Binding of the hormone to the receptor causes the complex to shift from the cytoplasm to the nucleus
Act as regulators of gene expression

18. A steroid receptor has 3 functional domains
Hormone-binding domain
DNA-binding domain
Domain that interacts with coactivators to affect level of gene transcription
In its inactive state, the receptor typically cannot bind to DNA because an inhibitor protein occupies the DNA binding site
Binding of ligand changes conformation

19. Coactivators
Target cell’s response to a lipid-soluble cell signal can vary enormously, depending on the nature of the cell
Even the same type of cell may have different responses
Depends on coactivators present
Estrogen has different effects in uterine tissue than mammary tissue
Not presence or absence of receptor
Presence or absence of coactivator

20. Receptor Kinases
Protein kinases phosphorylate proteins to alter protein function
Receptor tyrosine kinases (RTK)
Influence cell cycle, cell migration, cell metabolism, and cell proliferation
Alteration to function can lead to cancer
Membrane receptor
Plants possess receptors with a similar overall structure and function

21. When a ligand binds, dimerization and autophosphorylation occur
RTKs have
A single transmembrane domain
Anchors them in membrane
Extracellular ligand-binding domain
Intracellular kinase domain
Catalytic site of receptor acts as protein kinase
When a ligand binds, dimerization and autophosphorylation occur
Cellular response follows – depends on cellular response proteins

23. Insulin receptor
Activated receptor has phosphorylated sites that allow docking
Insulin is a hormone that helps to maintain a constant blood glucose level
Lowers blood glucose

24. Kinase cascade Mitogen-activated protein (MAP) kinases
Important class of cytoplasmic kinases
Mitogens stimulate cell division
Activated by a signaling module called a phosphorylation cascade or kinase cascade
Series of protein kinases that phosphorylate each other in succession
Amplifies the signal because a few signal molecules can elicit a large cell response

27. G-Protein Coupled Receptors
G-protein – protein bound to GTP
G-protein-coupled receptor (GPCRs) – receptors bound to G proteins
-G-protein is a switch turned on by the receptor
-G-protein then activates an effector protein (usually an enzyme)

28. Scaffold proteins
Thought to organize the components of a kinase cascade into a single protein complex
Binds to each individual kinase such that they are spatially organized for optimal function
Benefit in efficiancy
Disadvantage in reducing amplification effect

29. Ras proteins Small GTP-binding protein (G protein)
Link between the RTK and the MAP kinase cascade
Ras protein is mutated in many human tumors, indicative of its central role in linking growth factor receptors to their cellular response
Ras can regulate itself – stimulation by growth factors is short-lived

31. G-Protein Coupled Receptors
Single largest category of receptor type in animal cells is GPCRs
Receptors act by coupling with a G protein
G protein provides link between receptor that receives signal and effector protein that produces cellular response
All G proteins are active when bound to GTP and inactive when bound to GDP
Effector proteins are usually enzymes

33. Often, the effector proteins activated by G proteins produce a second messenger
2 common effectors
Adenylyl cyclase
Produces cAMP
cAMP binds to and activates the enzyme protein kinase A (PKA)
PKA adds phosphates to specific proteins
Phospholipase C
PIP2 is acted on by effector protein phospholipase C
Produces IP3 plus DAG
Both act as second messengers

36. Calcium
Ca2+ serves widely as second messenger
Intracellular levels normally low
Extracellular levels quite high
Endoplasmic reticulum has receptor proteins that act as ion channels to release Ca2+
Most common receptor binds IP3

37. Cell-to-Cell Interactions
Cells can identify each other by cell surface markers
-Glycolipids are commonly used as tissue-specific markers
-Major histocompatibility complex (MHC) proteins are used by cells to distinguish “self” from “nonself”

38. Different receptors can produce the same second messengers
Hormones glucagon and epinephrine can both stimulate liver cells to mobilize glucose
Different signals, same effect
Both act by same signal transduction pathway

40. Receptor for epinephrine has 9 isoforms
Single signaling molecule can have different effects in different cells
Existence of multiple forms of the same receptor (subtypes or isoforms)
Receptor for epinephrine has 9 isoforms
Encoded by different genes
Sequences are similar but differ in their cytoplasmic domains
Different isoforms activate different G proteins leading to different signal transduction pathways