Lecture 9: The Postsynaptic Density Flashcards
Which proteins are clustered immediately opposite release sites or active zones at synapses? What are these proteins known as?
ligand gated ion channels, anchoring proteins, cytoskeleton and regulatory proteins
these proteins are known as density because they appear to be dense in electron microscopy
What does the PSD core consist of?
high concentration of PSD-95
What is PSD95 orientated with? What does this suggest?
the N-terminus near the plane of postsynaptic membrane and the C-terminus deep in the spine
this close apposition suggests that PSD-95 is in a position to bind neurotransmitter receptors
What is the PSD pallium?
deeper layer, containing a scaffold of Shank and Homer proteins
What happens to the pallium during intense synaptic activity?
becomes denser and more prominent due to reversible addition of calcium calmodulin, Kinase II and other proteins
How many proteins do excitatory synapses have in the brain?
more than 1000 different proteins
How many proteins do inhibitory synapses have in the brain?
at least 250 different proteins
What are MAGUKs? What is an example of a MAGUK?
membrane-associated guanylate kinases
PSD-95 is the most abundant MAGUK at the mammalian PSD
What are GKAPs?
guanylate kinase-associated proteins also known as PSD-95 associated protein
What are SHANKs?
SH3 and multiple ankyrin repeat domains protein
What are Homer proteins also called?
VesI, cupidin and PSD-Zip45
What are many PSD proteins involved in?
cell adhesion
What are many PSD proteins also known as?
CAMs (cellular adhesion molecules)
What is a neuroligin?
a cell adhesion protein on the postsynaptic membrane that mediates the formation and maintenance of synapses between neurons.
What is a neurexin?
a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse - neuroligins act as ligands for Beta-neurexins
Where are neurexins located? How many transmembrane domains do they contain?
mostly on the presynaptic membrane and contain a single transmembrane domain
What is the role of a neuroligin? What does it act as a ligand for?
mediates the formation and maintenance of synapses between neurons
also act as ligands for β-neurexins, which are cell adhesion proteins located presynaptically
Where is neuroligin 1 characteristically found?
in all glutamatergic synapses and some nicotinic synapses in the peripheral nervous system
Where is neuroligin 2 characteristically found?
found preferentially in some inhibitory synapses (GABA) and in some cholinergic (acetylcholine) synapses
Where is neuroligin 3 characteristically found? What does neuroligin 3 form with neuroligin 1?
in excitatory and inhibitory synapses
heterodimers
Where is neuroligin 4 characteristically found?
found preferentially at glycinergic synapses in retina
What do neuroligins bind to?
postsynaptic density protein 95
How many PDZ binding domains does PSD95 have? What does PDZ mean?
three
P = PSD-95
D = Drosophila disc large tumor suppressor
Z = Zona occludens protein
How many amino acids in the PDZ motif?
80-90 amino acids
How do neuroligins bind to PSD95?
via 3rd PDZ domain
How does PSD95 bind AMPA glutamate receptors?
via 1st PDZ domain
Which interaction holds AMPA receptors in place?
neuroligin/neurexin interaction
What are the different things PSD95 bind to?
NMDA receptors, calcium-calmodulin protein kinase II, neuronal nitric oxide synthase and shank proteins, indirectly via GKAP
How does PSD-95 bind to a number of partners?
via the PDZ domains
How do post-synaptic specialisations regulate pre-synaptic specialisations and vice versa? What is a major example?
via CAMs
major example is the neurexin-neuroligin interaction
What happens when neuroligin is deleted?
this does not prevent synapse formation as other cell adhesion molecules can substitute
What do postsynaptic densities include?
dozens of signal transduction molecules including glutamate receptors, tyrosine kinase receptors and many intracellular signal transduction molecules e.g. protein kinase CaMKII
What are Shanks?
cytoskeletal proteins which couple via contact into the actin cytoskeleton
How do Shanks bind to the actin cytoskeleton?
bind via Homer to metabotropic glutamate receptors
also via Homer to IP3 receptors on the SER
What is gephyrin? What is it specific for?
key organising molecule specific for GABA and glycinergic synapses
How and what does gephyrin interact with?
self-assembles into a hexagonal lattice and interacts with various inhibitory synaptic proteins
What are both GABA and glycine receptors from the same superfamily as? What are the characteristics of all these receptors?
the nicotinic acetylcholine receptor
pentameric transmembrane proteins which contain at least 2 ɑ-subunits