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what is cytoskeletal proteins-linker proteins
PSD-95 proteins (aka MAGUK protein)
PSD-95 contains 5 protein-binding domains
- 3 amino-terminal PDZ (PSD-95, Discs-large, ZO-1),
- SH3 domain
- GK domain
what are the 4 classes of proteins and whats their function?
- plasma membrane proteins
- cytoskeletal proteins
- signaling proteins
- linker proteins
- ---all conspire to regulate complex functions (LTP, LTD)
Explain how PSD-95 binds to other PSD components
- PSD-95 binds nNOS via PDZ-PDZ interaction holding NOS in appropriate ositive to sense Ca2+ influx thru NMDA receptor channel opening.
- 3rd PDZ domain of PSD-95 binds SynGAP providing link between NMDAR and MAPK pathway
- ---ischemic challenge
- ---intercellular communication
what are the proposed functions of PSD?
- PSD formed early during synaptogenesis
- synaptic activity affects PSD morphology
- synaptic plasticity
what is PSD?
- dense are on tip of spine head (10-15%)
- membrane disk localizing glutamate receptors, anchors protein kinases, and other signaling molecules associated wit plasticity of synapses
- anchoring NMDA and AMPA receptors
- focuses synaptic signal, which increases efficiency, accuracy and speed
whats the most abundant in PSD?
explain the model for regulation of dendritic spine development
(PSD protein dynamics druing synaptogenesis)
- dendrites send out long thin processes (filopodia) that seek out and form synapses with nearby axons. fomration of filopodia is stimulated by high levels of synaptic activity or by profound inactivity, presmably in conjunction with local secreted factors.
- postsynaptic PDZ proteins are critical for development of filopodia to mature spines reprsentative mature mushroom-shaped spine
- maintenance of mature spines depends on low level stimulation of AMPA receptor
AMPA and NMDA thought to...
contribute to synaptic plasticity
PSD 95 family members may ...
stabilize the NMDA receptors arrayed in center of PSD while allowing AMPA receptors arrayed around periphery to turn over more quickly
decreasing surface of spine means?
more focus to receive nt
PSD 95 known to...
- last for only few hrs.
- -movement of PSD 95 may maintain size and strength
spinese appear and disppear on daily basis is ocnsistent with?
- high rates of synaptic formation and elimination during developmental stage in mice
- dendritic spines and PSDs are quite stable around second postnatal week
- stabilization conserves sizes of spines
with increasing develomental age...
- PSD 95 are bound to PSDs for approxi. an hr, sig. shorter than lifetime of dendritic spines and their PSDs and the PSD 95
- -PSD95 became less dynamic in dendritic spines
- PSDs decr. as development time increase
- retention time in PSDs incr.
what mechanisms keep PSD95-paGFP, thus determining the retention time?
- 1) unbinding of PSD95 from PSD
- 2) PSD95 could be trapped in spine head of diffusional compartmentalization by narrow spine neck
what is paGFP-actin?
depend on cycling of actin in dendritic spinces
results of paGFP, retention time?
- retention time for paGFP 1000x shorter than PSD95-paGFP and independent of development age
- paGFP increased with spine volume
- retention time for paGFP-actin was intermediate
are PSD 95 exchanged between PSDs in differ spines?
- spread of PSD 95 was bidirectional and didn't involve obvious transport particles;
- PSD95-paGFP spread rapidly over small distances
How does PSD 95 spread?
- by diffusion from PSD to PSD
- PSDs share common pool of PSD95
- after PSD95 unbinds from PSD, rapidly diffuses along dendritic shaft til captured by other PSDs
results review! about PSD-95
- retained by individual PSDs for very short time
- unbinds and diffuses rapidly within dendrite and binds to other PSDs
- visit dozens of PSDs before degradation; synapses are sharing dendritic PSD-95
- larger spines = long retention times
more of PSD 95 binders than PSD-95 means?
PSD-95 levels determmines...
synaptic strength and when combined with other PSD molecules determine synaptic size
redistribution of PSD-95...
- play role in synaptic plasticity
- contributes to induction and maintenance of LTP