molecular signaling within neurons Flashcards
3 forms of chemical signaling
synaptic
paracrine
endocrine
synaptic signaling
transfers info from one neuron to another through synaptic cleft, neurotransmitters, and receptors
paracrine signaling
acts over a longer range and involves the secretion of chemicals onto a group of nearby target cells
ex. clotting factors
endocrine signaling
secretion of hormones into the bloodstream
3 components of chemical signaling
- molecular signal transmits info from one cell to another
- a receptor molecules transduces the info
- a target molecule mediates the cellular response
advantages of chemical signaling
- 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)
3 classes of cell signaling molecules
- cell-impermeant: neurotransmitters and receptors
- cell-permeant: act on intracellular receptors (permeable, ex. steroids)
- cell-associated: attached to extracellular surface (ex. integrins)
categories of cellular receptors
- 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
heterotrimeric G-protein
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
cAMP produced when
g-proteins activate adenylyl cyclase
cGMP produced when
g-proteins activate guanylyl cyclase
kinases
transfer phosphate groups from ATP to serine, threonine, and tyrosine residues on target proteins, thereby regulating their activation status
phosphatases
do opposite of kinases, remove phosphates from target proteins
cAMP-dependent protein kinase
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
calcium/calmodulin-dependent protein kinase II (CaMKII)
composed of subunits which contain both catalytic and regulatory domains
binding of calcium bound calmodulin displaces the regulatory domain from the catalytic domain
protein kinase C (PKC)
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
why have dendritic spines?
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
cAMP response element binding protein (CREB)
transcription factor activated by a number of kinases
activation is maintained through inhibition of a protein phostase 1 and 2a
nerve growth factor (NGF)
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
brain derived neurotrophic factor (BDNF)
another member of the neurotrophin family
binds to the receptor tyrosine kinase TrkB
cerebellar long-term depression (LTD)
- 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
