Chapter 9 Cell Communication

Bonus topics: calmodulin cholera toxin scaffold proteins

Communication between cells requires:

ligand = the signaling molecule receptor protein:
the molecule to which the receptor binds may be on the plasma membrane or within the cell

when a ligand binds to a receptor protein, the cell has a response = signal transduction
Fig. 9.1
2

 signaling is defined by the distance from the source to the receptor four basic mechanisms for cellular communication:
1. direct contact 2. paracrine signaling 3. endocrine signaling 4. synaptic signaling

Fig. 9.2
3

Direct contact: molecules on the surface of one cell are

recognized by receptors on the adjacent cell

Paracrine signaling: signal released from a cell has an

effect on neighboring cells

Endocrine signaling: hormones released from a cell

affect other cells throughout the body

Synaptic signaling: nerve cells release the signal

(neurotransmitter) which binds to receptors on nearby cells

Signal transduction:
the events within the cell that occur in response to a signal different cell types can respond differently to the same signal a cells response to a signal often involves activating or inactivating proteins phosphorylation (or dephosphorylation) is a common way to change the activity of a protein enzyme-mediated: protein kinase: adds a phosphate to a protein phosphatase: removes a phosphate from a protein Adding and removing phosphates is a very common way to turn pathways on or off
Fig. 9.3

Receptor Types receptors can be defined by their location

intracellular receptor: located within the cell cell surface receptor (membrane receptor): located on the plasma membrane to bind a ligand outside the cell Three subclasses of membrane receptors: 1. channel linked receptors:
ion channel that opens in response to a ligand

2. enzymatic receptors:
receptor is an enzyme that is activated by the ligand

3. G protein-coupled receptor:
a G protein (bound to GTP) assists in transmitting the signal

channel linked receptors: integral membrane protein ion channel that opens in response to a ligand chemically gated

enzymatic receptors: integral membrane protein binds ligand on extracellular domain catalytic domain on cytoplasmic side Is an enzyme that is activated by the ligand
Fig. 9.4
7

G protein-coupled receptor (GPCR):

a G-protein assists in transmitting the signal indirectly activated ion channels or enzymes receptor (GPCR) has an inactive G-protein bound on cytoplasmic domain when ligand binds to GPCR, GDP stuck on the G-protein is phosd to GTP (activates G-protein) activated G-protein activates effector (enzyme or channel)

Fig. 9.4
8

Intracellular Receptors
steroid hormones
have a nonpolar, lipid-soluble structure can cross the plasma membrane to a steroid receptor usually affect regulation of gene expression an inhibitor blocks the receptor from binding to DNA until the hormone is present

A steroid receptor has 3 functional domains: 1. hormone-binding domain 2. DNA binding domain 3. domain that interacts with coactivators to affect gene expn
Fig. 9.5

Receptor Kinases
receptor tyrosine kinases
membrane receptor when bound by a ligand, the receptor is activated by dimerization and autophosphorylation activated receptor adds a phosphate to tyrosine on a response protein an example is the insulin receptor

Fig. 9.7

10

Fig. 9.6
11

kinase cascade: a series of protein kinases that phosphorylate each other in succession amplifies the signal because a few signal molecules can elicit a large cell response mitogen-activated protein (MAP) kinases are activated by kinase cascades

Fig. 9.8

12

G Protein-Coupled Receptors
G protein = protein bound to GTP G protein-coupled receptor (GPCR) = receptor bound to G protein
G protein is a switch turned on by the receptor G protein then activates an effector protein usually an enzyme sometimes an ion channel

Fig. 9.11

13

RTK RAS MAPKs

Fig. 9.10
14

GPCR effectors multiple second messengers

once activated, the effector protein produces a second messenger second messenger generates the cellular response to the original signal example: one common effector protein is adenylyl cyclase which produces cAMP as a second messenger other second messengers: inositol phosphates, calcium ions (Ca2+)

15

cAMP signaling pathway

Fig. 9.13

first messenger? second messenger?

Inositol phospholipid signaling

first messenger? second messenger?
Fig. 9.15
16

Different receptors can activate the same signaling pathways

example: epinephrine and glucagon bind GPCRs that produce cAMP resulting in glycogenolysis

Fig. 9.17

17

Complexity = flexibility
different receptors can produce the same second messengers receptor subtypes can lead to different effects in cells GPCRs and RTKs can activate the same pathways
nine GPCR subtypes for epinephrine different G proteins

18