chapter 8 - post-synaptic organization Flashcards
8.1. [postsynaptic organization] how are excitatory and inhibitory postsynaptic densities organized?
reproduce drawing for both
Postsynaptic organization of synapses
> postsynaptic side of the synapse: specialized to receive the NT signal released from the presynaptic terminal and transduce it into electrical and biochemical changes in the postsynaptic cell
> ionotropic NT receptors (=ligand-gated receptor channels) are the cardinal functional components of postsynaptic specializations. These receptor channels are embedded in a dense protein network of:
* anchoring and scaffolding molecules
* signaling enzymes (e.g. kineases, phosphatases)
* cytoskeletal components
* other membrane proteins (Ttranssynaptic / cell-adhesion molecules)
> excitatory and inhibitory postsynaptic specializations differ significantly from each other in terms of molecular organization
Postsynaptic density (PSD) of excitatory synapses
* PSDs are usually located at dendritic spines and contain glutamate receptors AMPA, NMDA)
> Roles of PSDs:
* mediate apposition of pre- and postsynaptic membranes
* cluster postsynaptic receptors
* couple the activation of postsynaptic receptors to biochemical signaling events in the postsynaptic neuron
> PSDs are held together by cytoplasmic actin filaments
Inhibitory synapses are mainly formed on the shaft of dendrites or around the neuronal cell body, and by EM, they show only a slight electron-dense thickening associated with the postsynaptic membrane and hence were described as symmetric (type II) synapses. This presumably reflects the fact that the inhibitory postsynaptic specialization is much less elaborate than the PSD of excitatory synapses.
The cardinal neurotransmitter receptors of central inhibitory synapses are the GABAA receptors and glycine receptors. These receptors interact directly with gephyrin, a well-known postsynaptic scaffold protein of inhibitory synapses
8.2. [postsynaptic organization] which classes of molecules are involved? Provide examples for each class.
PSD scaffold proteins and their functional domain
> scaffold proteins bind to and tether or stabilize various membrane proteins and signaling molecules, thereby facilitating coupling of NT receptors with downstream signaling molecules in the PSD
> PDZ Functional domains, typically mediate, protein-protein interactions
Act: actin-binding
Ank: ankyrin repeats
ArfGAP: GTPase-activating protein from Arf small GTPase
CC: coiled coil
CH: calponin homology
CK: calmodulin-dependent kinase (CaMK)-like domain
CRIB: Cdc42/Rac interactive-binding
Efh: EF-hand
EVH1: Ena/VASP homology 1
GH1: GKAP homology
GK: guanylate kinase-like domain
GKBD: GKAP-binding domain
GRKBD: GRK2-binding domain
GTP-CDC: GTP-cell division protein
L27: domain initially found in LIN-2 and LIN-7
LRR: leucine-rich repeat
PH: pleckstrin homology
RapGAP: GTPase-activating protein for Rap small GTPases RasGAP: GTPase-activating protein for Ras small GTPases
RBC: Rac binding
SAM: sterile alpha motif
SHD: Spa2 homology domain
Spectrin: spectrin repeat
ST: subcellular targeting domain
WW: domain with two conserved Trp (W) residues
PSD proteins linked to brain diseases
> ASDs have been linked to mutations in genes encoding Shank2 and Shank3, PSD-93, PSD-95, DLGAP2/SAPAP2, and SynGAP1, as well as synaptic adhesion molecules neuroligin 3, neuroligin 4, and neurexin 1
≥ Mutations in SAPAP3 are associated with obsessive compulsive
*disorder
