mPins modulates PSD-95 and SAP102 trafficking and influences NMDA receptor surface expression

Abstract

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.

A specific role of AGS3 in the surface expression of plasma membrane proteins

“…Several previous studies have implicated mPins in tuning synaptic plasticity via regulating the trafficking of NMDA receptor or the activity of G protein-activated inwardly rectifying potassium channels in hippocampal neurons (17,39). Our current findings raise the exciting possibility that AGS3 and mPins may constitute a family of important modulators of neural plasticity.…”

“…The close homolog of AGS3, mPins, has been shown to promote the surface expression of NMDA receptors via its interaction with PDZ domain-containing proteins (17). Because members of the Kir2 family can bind to PDZ proteins at their C termini (23), we wondered whether the effect of AGS3 on the trafficking of Kir2.1 is linked to PDZ proteins.…”

“…Second, one major interacting partner of AGS3, G␣i3, is localized primarily at the Golgi apparatus (15,16). Third, the mammalian homolog of Drosophila melanogaster partner of inscuteable (mPins), a protein closely related to AGS3, was recently shown to interact with two members of the PDZ-domain containing protein family, PSD-95 and SAP102, and promotes the surface expression of NMDA receptors in neurons (17). Based on these observations, we examined whether AGS3 functions in membrane trafficking.…”

Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module

“…This is achieved through direct binding of Scribble to this GPCR and requires signalling from Scribble through b-Pix/GIT1/ARF6. Downstream from GPCRs, mammalian Lgl2 and Dlg family members, have also been shown to interact with the regulator of GPCR signalling, mPins (Sans et al, 2005;Yasumi et al, 2005 and see also Januschke and Gonzalez, 2008). The genetic interaction of mPins and Scribble/Dlg/Lgl is conserved in Drosophila, with pins itself being a potent tumour suppressor in Drosophila brain neuroblasts (Lee et al, 2006).…”

NS21: Re-defined and modified supplement B27 for neuronal cultures

“…Such supplements were widely welcomed. Particularly B27 is used by many investigators for a number of different neuronal culture systems (Christopherson et al, 2005;Colledge et al, 2003;Craven et al, 1999;Deisseroth et al, 1996;El-Husseini et al, 2000;Mi et al, 2004;Passafaro et al, 2003;Pratt et al, 2003;Roche et al, 2001;Sans et al, 2005;Schluter et al, 2006;Stellwagen and Malenka, 2006;Tai et al, 2007;Thiagarajan et al, 2002;Tomita et al, 2004;Tsui and Malenka, 2006;Ullian et al, 2001). …”