molecular signaling in neurons

intracellular signal transduction

cascade of events inside the cell

signal amplification

a single molecule of a neurotransmitter binding to its receptor can generate many thousands of second-messenger molecules

amplification in signal transduction pathways

1. receptor

amplification

2. g-proteins

no amplification

3. adenylyl cyclase

amplification

4. cyclic amp

no amplification

5. protein kinases

amplification

6. phosphate transferred to target proteins

types of chemical signaling

1. synaptic

2. paracrine

- secretion of signal to nearby cells; longer range than synaptic

3. endocrine

- secretion of hormones into the bloodstream; targets throughout the body

be able to recognize figures!! (fig 7.1)

general pathway of chemical signaling

1. signaling cell

2. signal

3. receptor

4. effector molecule

5. response

classes of cell signaling molecules

1. cell-impermeant molecules

2. cell-permeant molecules

- can cross plasma membrane on their own

3. cell-associated molecules

- signaling molecules are anchored to outer part of cell

recognize figure 7.3!!

categories of cellular receptors

A) Channel-linked receptors

1. signal binds

2. channel opens

3. ions flow across membrane

B) enzyme-linked receptors

1. signal binds

2. enzyme activated

3. enzyme generates activated effector

C) G-protein coupled receptors

1. signal binds

2. G-protein binds to receptor

3. G-protein activated

D) Intracellular receptors

1. signal binds

2. activated receptor regulates transcription

types of G proteins

1. heterotrimeric g-proteins

2. monomeric g-proteins

heterotrimeric g-protein

it is a G- protein consisting of three subunits (alpha, beta, and gamma). When a hormone binds, a GDP bound to the alpha subunit dissociates and a GTP associates, and the alpha subunit dissociates from the beta and gamma subunits.

figure 7.5

monomeric g-proteins

- contain only one protein

- activated by number of receptors that activate GEF activity

- GEFs add GTP to ras protein and activate them

figure 7.5

effector pathways associated with g-protein coupled receptors

1. neurotransmitter

2. receptor

3. g-protein

4. effector protein

5. second messengers

6. later effectors

7. target action

effector proteins associated with g-protein coupled receptors

adenylyl cyclase and phospholipase c

second messengers associated with g-protein coupled receptors

cAMP, diaglycerol, IP3

later effectors associated with g-protein coupled receptors

protein kinase a, protein kinase c, ca2+ release

role of ca2+ as a signaling molecule

watch animation on canvas

- ca2+ acts as a second messenger

kinases

proteins that phosphorylate other proteins

- activated by second messengers

- use ATP to transfer a phosphate group

phosphatases

remove phosphates from proteins to alter their activity

- activated by second messengers

regulation of transcription/gene expression

- multiple signaling pathways converge by activating kinases that phosphorylate CREB (kinases: PKA, Ca2+/calmodulin kinase IV, MAPK)

- phosphorylation of CREB lets it bind to co-activators that stimulate RNA pol to begin synthesis of RNA

- RNA transcribed and exported to cytoplasm for translation into protein

figure 7.12

Nerve Growth Factor (NGF) Signal Transduction

- NGF works by binding to a tyrosine-kinase receptor (TrkA)

- required for differentiation, survival, and connectivity of neurons

be able to recognize figure 7.13

tyrosine hydroxylase signal transduction

1. action potential

2. ca2+ influx

3. activation of second messengers

4. activation of protein kinases

5. tyrosine hydroxylase phosphorylated

6. increase in catecholamine synthesis

7. increase in transmitter release

figure 7.15