Wikinotes

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while there are ~10 classical transmitters, there are over 100 neuropeptides
neuropeptides ; made from protein precursors encoded by genes
classical transmitter: made by enzymes in cytosol
- except dopamine b-hydroxylase in vesicles
neuropeptide in dense-cored vesicles (regulated secretory vesicles) that need to be made.
classical transmitter in synaptic vesicles that can be reused.
while neuron have one classical transmitter, they can have multiple neuropepties

neureptide precursor
- cleavage sites
- glycine for amidation : to protect it from degradation
- a signal sequence for transport to ER, but so far not well-defined
as precursor so that
- they can be big enough to be inserted into ER co-translationally
- flexibility: one precurosor can generate multiple pepties or different isoforms
neuropeptides are evolutionarily older than classical transmitters: used as signaling before neurons exist (ex: yeast mating peptides)
can be transported to Golgi for glycosylatio and sulfation, sorted into transport vesicles, and then cleaved from the precursors
- cleavage can occur in trans-golgi network, like by furin
processing
- signal sequence cleavage in ER
- endoproteolytic cleavage in TGN (by furin) or secretory vesicle (by PCs)
- carboxypeptidase (in secretory vesicle)
- peptidyl-glycine-a-amidation
- amide is put on
sorting into regulated secretory vesicles
- prehaps by aggregation and drop in pH triggers aggregation of protease and other aggregation-related proteins, but not clear

slow transmission via G protein-linked receptor
useful anatomical markers to define subsets of neurons
used widely by neuroendocine cells in hypothalamus
- ex: vasopressin and oxytocin
neuropeptides are modulatory : often acts as a feedback control
play a role in homeostasis, stress, reproduction
also modulate behaviour : ex, like whether C-elegans like to eat together or not
other specific roles
- opioids : inhibit pain
- neuropeptide Y, ghrelin : eating
- orexin : sleep
- GRP (gastrin-related peptide) : GRP has to do with formation fo memory to fear
use slow synaptic transmission
- slow transmission, alter the potential fo cells by regulating ion channels, or other properties like cytoskeletal dyanmics

7-transmembrane domains
cytosolic terminal : regulates the receptor like turning it off, densentization, internalization
- also site for G-protein binding and other downstream effects
three subunits
- alpha, beta and gamma (always linked to beta)
- alpha is the G protein that binds to GTP
- they're effectors, Gbeta-gamma can be released to do downstream effects

Adenylate cyclase
- make cAMP
- regulate cAMP dependent protein kinase (PKA)
phospholipase C
- make IP and DAG
- release calcium from internal storage
ion channels
- Ga or G-beta-gamma can binds directly to the channel
- or second messenger binds to channel cand causes phosphorylation
cyclic GMP phosphodiesterase, esp for vision

G protein ligands
- neurotransmitters: classical and neuropeptides
- sensory inputs, lipids, cytokines
specificity
- determined by the subtype
  - beta adrenergic receptors bind to Gs and activates adenylate cyclase
  - alpha adrenergic receptors bind to Gi and does the opposite
- one transmitter can have multiple receptors and oppsite effect on different G proteins
histamine:
- binds H1 receptor -> sleepiness
- H2 receptor -> allergies

neuropeptides can change synpatic strength
slow EPSP : closing resting K+ channels or opening resting cation channels
slow IPSP : resting K+ channels opening are affected
shape of action potential : closing of voltage gated K channels or opening of voltage gated Ca channels
size of PSP : ligand-gated ion channels and changes in transmitter release
can also change resting membrane potential
fine-tune neuronal responses

Tuesday, March 18, 2014
Neuropeptide