mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression.
Appropriate trafficking and targeting of glutamate receptors (GluRs) to the postsynaptic density is crucial for synaptic function. We show that mPins (mammalian homologue of Drosophila melanogaster partner of inscuteable) interacts with SAP102 and PSD-95 (two PDZ proteins present in neurons), and functions in the formation of the NMDAR-MAGUK (N-methyl-D-aspartate receptor-membrane-associated guanylate kinase) complex. mPins enhances trafficking of SAP102 and NMDARs to the plasma membrane in neurons. Expression of dominant-negative constructs and short-interfering RNA (siRNA)-mediated knockdown of mPins decreases SAP102 in dendrites and modifies surface expression of NMDARs. mPins changes the number and morphology of dendritic spines and these effects depend on its Galphai interaction domain, thus implicating G-protein signalling in the regulation of postsynaptic structure and trafficking of GluRs.
Sans
Nathalie
N
Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Building 50, Room 4146, 50 South Drive, Bethesda, MD 20892-8027, USA. nathalie.sans@bordeaux.inserm.fr
Wang
Philip Y
PY
Du
Quansheng
Q
Petralia
Ronald S
RS
Wang
Ya-Xian
YX
Nakka
Sajan
S
Blumer
Joe B
JB
Macara
Ian G
IG
Wenthold
Robert J
RJ
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins; D002462:Cell Membrane; D003712:Dendrites / Q000737:chemistry; D000076122:Disks Large Homolog 4 Protein; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000502:physiology; D051528:Guanylate Kinases / Q000378:metabolism; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009474:Neurons; D009479:Neuropeptides / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C502655:LGN protein, mouse; D008565:Membrane Proteins; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; C491075:Dlgh3 protein, mouse; D051528:Guanylate Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go