molecular signaling within neurons

Question 1

3 forms of chemical signaling

Answer 1

synaptic
paracrine
endocrine

Question 2

synaptic signaling

Answer 2

transfers info from one neuron to another through synaptic cleft, neurotransmitters, and receptors

Question 3

paracrine signaling

Answer 3

acts over a longer range and involves the secretion of chemicals onto a group of nearby target cells
ex. clotting factors

Question 4

endocrine signaling

Answer 4

secretion of hormones into the bloodstream

Question 5

3 components of chemical signaling

Answer 5

1. molecular signal transmits info from one cell to another
2. a receptor molecules transduces the info
3. a target molecule mediates the cellular response

Question 6

advantages of chemical signaling

Answer 6

• amplification: individual signaling reactions generate a larger number of molecular products than those that initiated the reaction
• specificity: multiple levels of molecular interactions allows the cell to fine tune its response (when and how it responds)

Question 7

3 classes of cell signaling molecules

Answer 7

• cell-impermeant: neurotransmitters and receptors
• cell-permeant: act on intracellular receptors (permeable, ex. steroids)
• cell-associated: attached to extracellular surface (ex. integrins)

Question 8

categories of cellular receptors

Answer 8

• channel-linked (ionotropic): receptor and transducing functions part of the same molecule, receptor forms an ion channel pore
• enzyme-linked: intracellular domain is an enzyme whose catalytic activity is regulated by ligand binding
• G-protein-coupled receptors: regulate intracellular reactions indirectly through GTP-binding proteins (ex. dopamine and serotonin receptors)
• intracellular receptors: activated cell-permeant signaling molecules, often lead directly to a gene expression by way of DNA-binding domain exposed by ligand binding

Question 9

heterotrimeric G-protein

Answer 9

composed of 3 subuntits
binding of alpha unit to GTP dissociates it from other subunits, allowing them to bind downstream effectors
G-protein signaling terminated by hydrolysis of GTP to GDP

Question 10

cAMP produced when

Answer 10

g-proteins activate adenylyl cyclase

Question 11

cGMP produced when

Answer 11

g-proteins activate guanylyl cyclase

Question 12

kinases

Answer 12

transfer phosphate groups from ATP to serine, threonine, and tyrosine residues on target proteins, thereby regulating their activation status

Question 13

phosphatases

Answer 13

do opposite of kinases, remove phosphates from target proteins

Question 14

cAMP-dependent protein kinase

Answer 14

tetrameric complex of two catalytic subunits and two regulatory subunits
cAMP activates PKA by binding to the regulatory subunits and causing them to release the catalytic subunits

Question 15

calcium/calmodulin-dependent protein kinase II (CaMKII)

Answer 15

composed of subunits which contain both catalytic and regulatory domains
binding of calcium bound calmodulin displaces the regulatory domain from the catalytic domain

Question 16

protein kinase C (PKC)

Answer 16

activated by DAG and calcium
binding of DAG causes PKC to translocate to the plasma membrane, where it also binds calcium and the membrane phospholipid phosphatidylserine, relieving its autoinhibition

Question 17

why have dendritic spines?

Answer 17

serve as a diffusion barrier
- increase in calcium induced by synaptic activity is confined to the spine
also serve as reservoirs for signaling proteins, many of which are contained in the postsynaptic density

Question 18

cAMP response element binding protein (CREB)

Answer 18

transcription factor activated by a number of kinases
activation is maintained through inhibition of a protein phostase 1 and 2a

Question 19

nerve growth factor (NGF)

Answer 19

member of the neurotrophin family - involved in differentiation, survival, and synapse formation
NGF binding causes the TrkA receptor to dimerize, resulting first in autophosphorylation of the receptor followed by phosphorylation of downstream signaling molecules

Question 20

brain derived neurotrophic factor (BDNF)

Answer 20

another member of the neurotrophin family
binds to the receptor tyrosine kinase TrkB

Question 21

cerebellar long-term depression (LTD)

Answer 21

• glutamate released at synapses btw parallel fibers and purkinje neurons, in addition to providing depolarization to opening of AMPARs, also activates metabotropic glutamate receptors which activate signaling molecules
• climbing fiber synapses provide more depolarization than parallel fiber synapses, leading to opening of voltage-gated calcium channels
• the simultaneous activation of climbing fiber and parallel fiber synapses leads to activation of PKC leading to weakening of parallel fiber synapses