Stargazin and Other Transmembrane AMPA Receptor Regulating Proteins Interact with Synaptic Scaffolding Protein MAGI-2 in Brain

Deng, Feilong; Price, Maureen G.; Davis, Caleb; Mori, Mayra; Burgess, Daniel L.

doi:10.1523/jneurosci.1851-06.2006

Cited by 75 publications

(69 citation statements)

References 59 publications

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“…The near-complete loss of podocytes and the rapid progression of glomerular disease in Magi-2 Δ/Δ mice are unusual and cannot be explained purely on the basis of nephrin reduction. These findings suggest an additional, nephrin-independent prosurvival role for MAGI-2 in podocytes, perhaps by blocking the proapoptotic signaling properties of dendrin (34), another MAGI-2 interacting protein (35).…”

Section: Discussionmentioning

confidence: 89%

MAGI-2 scaffold protein is critical for kidney barrier function

Balbas¹,

Burgess

Murali

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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MAGUK Inverted 2 (MAGI-2) is a PTEN-interacting scaffold protein implicated in cancer on the basis of rare, recurrent genomic translocations and deletions in various tumors. In the renal glomerulus, MAGI-2 is exclusively expressed in podocytes, specialized cells forming part of the glomerular filter, where it interacts with the slit diaphragm protein nephrin. To further explore MAGI-2 function, we generated Magi-2-KO mice through homologous recombination by targeting an exon common to all three alternative splice variants. Magi-2 null mice presented with progressive proteinuria as early as 2 wk postnatally, which coincided with loss of nephrin expression in the glomeruli. Magi-2-null kidneys revealed diffuse podocyte foot process effacement and focal podocyte hypertrophy by 3 wk of age, as well as progressive podocyte loss. By 5.5 wk, coinciding with a near-complete loss of podocytes, Magi-2-null mice developed diffuse glomerular extracapillary epithelial cell proliferations, and died of renal failure by 3 mo of age. As confirmed by immunohistochemical analysis, the proliferative cell populations in glomerular lesions were exclusively composed of activated parietal epithelial cells (PECs). Our results reveal that MAGI-2 is required for the integrity of the kidney filter and podocyte survival. Moreover, we demonstrate that PECs can be activated to form glomerular lesions resembling a noninflammatory glomerulopathy with extensive extracapillary proliferation, sometimes resembling crescents, following rapid and severe podocyte loss.

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Section: Discussionmentioning

confidence: 89%

MAGI-2 scaffold protein is critical for kidney barrier function

Balbas¹,

Burgess

Murali

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Mechanistically, functional cooperation might be mediated by postsynaptic connecting molecules interacting with both neuroligin-1 and N-cadherin. Postsynaptic scaffolding proteins binding to neuroligin-1 such as S-SCAM (MAGI-2) have been hypothesized to be able to link the two adhesion systems via binding to δ-catenin or β-catenin (25)(26)(27)(28)(29). To examine the potential role of S-SCAM, we expressed truncated forms of S-SCAM that were designed to inhibit protein interactions of S-SCAM in a dominant-negative manner.…”

Section: Resultsmentioning

confidence: 99%

“…The MAGI type postsynaptic scaffolding protein S-SCAM (26,29) has been described to potentially interact with catenins via binding with its PDZ5 domain to the PDZ-binding domains of β-catenin and δ-catenin (28,40). Furthermore, S-SCAM has been suggested to bind with its WW and PDZ1 domain to neuroligin-1 (27).…”

Section: Discussionmentioning

confidence: 99%

Essential cooperation of N-cadherin and neuroligin-1 in the transsynaptic control of vesicle accumulation

Stan¹,

Pielarski²,

Brigadski

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

117

116

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Cell adhesion molecules are key players in transsynaptic communication, precisely coordinating presynaptic differentiation with postsynaptic specialization. At glutamatergic synapses, their retrograde signaling has been proposed to control presynaptic vesicle clustering at active zones. However, how the different types of cell adhesion molecules act together during this decisive step of synapse maturation is largely unexplored. Using a knockout approach, we show that two synaptic adhesion systems, N-cadherin and neuroligin-1, cooperate to control vesicle clustering at nascent synapses. Live cell imaging and fluorescence recovery after photobleaching experiments at individual synaptic boutons revealed a strong impairment of vesicle accumulation in the absence of N-cadherin, whereas the formation of active zones was largely unaffected. Strikingly, also the clustering of synaptic vesicles triggered by neuroligin-1 overexpression required the presence of N-cadherin in cultured neurons. Mechanistically, we found that N-cadherin acts by postsynaptically accumulating neuroligin-1 and activating its function via the scaffolding molecule S-SCAM, leading, in turn, to presynaptic vesicle clustering. A similar cooperation of N-cadherin and neuroligin-1 was observed in immature CA3 pyramidal neurons in an organotypic hippocampal network. Moreover, at mature synapses, N-cadherin was required for the increase in release probability and miniature EPSC frequency induced by expressed neuroligin-1. This cooperation of two cell adhesion systems provides a mechanism for coupling bidirectional synapse maturation mediated by neuroligin-1 to cell type recognition processes mediated by classical cadherins.synapse maturation | synaptic adhesion molecules | vesicle clustering

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“…MAGI2 has been implicated in both glutamatergic (Deng et al, 2006) and GABAergic pathways (Sassoe-Pognetto et al, 2011). SNPs of MAGI2 have been associated with performance in the Wisconsin Sorting Card Test (WCST) in patients with SCZ (Koide et al, 2012), whereas in animal models it was shown to modulate long-term memory and associative learning (Emtage et al, 2009;Stetak et al, 2009).…”

Section: Discussionmentioning

confidence: 99%