cell communication chapter 9. 2 overview communication between cells requires –ligand –...
TRANSCRIPT
Cell CommunicationChapter 9
2
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
Ligand-Receptor
3
4
LIGANDS
5
Four basic mechanisms for cellular communication
1. Direct contact
2. Synaptic signaling
3. Paracrine signaling
4. Endocrine 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
• Animals• Nerve cells release
the signal (neurotransmitter) which binds to receptors on nearby cells
• Association of neuron and target cell is a chemical synapse
8
Synaptic 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
9
Paracrine 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
10
Endocrine signaling
11
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 (p. 170)– Glucagon example (p. 170)
Hormone: Epinephrine
• Flight or Fight
• Differing effects of epinephrine depend of the different cell types with receptors for this hormone, but different sets of proteins respond to that signal
• Liver – it mobilizes glucose
• Heart muscle-contract more forcefully
• Blood vessels-contract or dilate
12
Hormone: Glucagon
• A variety of cell respond the same way to control blood glucose
• Raise blood sugar
• Works on liver cells and adipose tissue
• Breaks down stored glycogen into glucose by turning on the genes that make the enzymes that synthesize glucose
13
14
Phosphorylation
• Addition of a 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 Don’t get confused!
15
Receptors
16
17
Receptor Types
• Receptors can be defined by their location
1. Intracellular receptor – located within the cell
2. 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
18
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
19
20
A steroid receptor has 3 functional domains
1.Hormone-binding domain
2.DNA-binding domain
3.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
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 but, the
Presence or absence of coactivator21
22
Cell Surface Receptors/ Membrane receptors
1. Chemically gated ion channels – channel-linked receptors that open to let a specific ion pass in response to a ligand
2. Enzymatic receptors – receptor is an enzyme that is activated by the ligand
– Almost all are protein kinases
3. G protein-coupled receptor – a G-protein (bound to GTP) assists in transmitting the signal from receptor to enzyme (effector)
23
Chemically gated ion channels
24
25
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
26
27
• Insulin is a hormone that helps to maintain a constant blood glucose level
• Glucose is bonded with other glucose molecules and converted to a glycogen molecule
• Lowers blood glucose28
Insulin receptor(… how RTK works to lower blood sugar)
• A single transmembrane domain• Anchors them in membrane
• Extracellular ligand-binding domain
• Intracellular kinase domain• Catalytic site of receptor acts as protein kinase
• Process: – When a ligand bind:
• dimerization and autophosphorylation occurs
– Cellular response follows – depends on cellular response proteins
29
Summary of RTKs
G-Protein Coupled Receptors
• G Proteins are transmembrane receptors
• Single largest category of receptor type in animal cells is GPCRs
30
31
G-Protein Coupled Receptors
• Sense molecules on OUTSIDE of cell (ligand)– Hormones, light sensitive compounds,
neurotranmsitters, pheromones, odors
• Activate a signal transduction INSIDE of the cell– ultimately leading to a response.– Open a gated channel– Enzymatic reaction
http://www.youtube.com/watch?v=NB7YfAvez3o
32
G-Protein
33
Smell you later…
34
Often, the effector proteins activated by G proteins produce a second messenger
2 common effectors
1.Adenylyl cyclase– Produces cAMP (helpful for hormones that cannot get
through cell membrane)– cAMP binds to and activates the enzyme protein kinase A
(PKA)– PKA adds phosphates to specific proteins
2.Phospholipase C– PIP2 is acted on by effector protein phospholipase C
– Produces IP3 plus DAG
– Both act as second messengers35
36
• http://www.rci.rutgers.edu/~uzwiak/AnatPhys/ChemicalSomaticSenses.htm
37
Different Signals, Same Effect
• 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
38
39
• 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
40