NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex

Sans, Nathalie; Prybylowski, Kate; Petralia, Ronald S.; Chang, Kai; Wang, Yaxian; Racca, Claudia; Vicini, Stefano; Wenthold, Robert J.

doi:10.1038/ncb990

Cited by 290 publications

(275 citation statements)

References 45 publications

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“…Brain of P1 Sprague Dawley rats were homogenized in PBS containing a mixture of protease inhibitors (Sans et al, 2001), and protein concentrations were measured using a BCA assay (Pierce, Rockford, IL). For immunoprecipitation experiments, rat brains were processed using sodium deoxycholate solubilization as described previously (Sans et al, 2003). Immunoprecipi- .…”

Section: Methodsmentioning

confidence: 99%

Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

Montcouquiol¹,

Sans²,

Huss³

et al. 2006

J. Neurosci.

285

287

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Section: Methodsmentioning

confidence: 99%

Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

Montcouquiol¹,

Sans²,

Huss³

et al. 2006

J. Neurosci.

285

287

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“…[24][25][26][27][28][29][30] In addition, binding of newly synthesized NMDA receptor subunits to PSD-95 or SAP102 links the receptor to different intracellular trafficking pathways, which is essential for its trafficking from the ER/Golgi complex to the PSD. [31][32][33][34] Changes in the expression of transcripts encoding NMDA receptor subunits in the prefrontal cortex have previously been described in post-mortem schizophrenic brains. [35][36][37] However, relatively little is known about protein expression of these subunits in schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

et al. 2006

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Abnormal expression of the N-Methyl-D-Aspartate (NMDA) receptor and its interacting molecules of the postsynaptic density (PSD) are thought to be involved in the pathophysiology of schizophrenia. Frontal regions of neocortex including dorsolateral prefrontal (DLPFC) and anterior cingulate cortex (ACC) are essential for cognitive and behavioral functions that are affected in schizophrenia. In this study, we have measured protein expression of two alternatively spliced isoforms of the NR1 subunit (NR1 C2 and NR1 C2 0 ) as well as expression of the NR2A-D subunits of the NMDA receptor in DLPFC and ACC in post-mortem samples from elderly schizophrenic patients and a comparison group. We found significantly increased expression of NR1 C2 0 but not of NR1 C2 in ACC, suggesting altered NMDA receptor cell membrane expression in this cortical area. We did not find significant changes in the expression of either of the NR1 isoforms in DLPFC. We did not detect changes of any of the NR2 subunits studied in either cortical area. In addition, we studied expression of the NMDAinteracting PSD molecules NF-L, SAP102, PSD-95 and PSD-93 in ACC and DLPFC at both transcriptional and translational levels. We found significant changes in the expression of NF-L in DLPFC, and PSD-95 and PSD-93 in ACC; increased transcript expression was associated with decreased protein expression, suggesting abnormal translation and/or accelerated protein degradation of these molecules in schizophrenia. Our findings suggest abnormal regional processing of the NMDA receptor and its associated PSD molecules, possibly involving transcription, translation, trafficking and protein stability in cortical areas in schizophrenia.

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“…Likewise, in the neuronal system, disruption of the exocyst function by exocyst subunit sec10 C-terminal deletion mutant overexpression and exocyst subunit sec5 knockout inhibited neurite outgrowth in neuroendocrine PC12 cells and cultured hippocampal neurons, respectively (11,16). In addition, the exocyst subunit sec8 has been shown to play a role in targeting the NMDA glutamate neurotransmitter receptor to the plasma membrane via its association with the PDZ-binding protein SAP102 in cultured hippocampal neurons (17). Finally, the exocyst has also been shown to promote protein translation and filopodia formation (18 -19).…”

mentioning

confidence: 99%

The Mammalian Exocyst, a Complex Required for Exocytosis, Inhibits Tubulin Polymerization

Wang

Liu

Adamson

et al. 2004

Journal of Biological Chemistry

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The exocyst is a 734-kDa complex essential for development. Perturbation of its function results in early embryonic lethality. Extensive investigation has revealed that this complex participates in multiple biological processes, including protein synthesis and vesicle/ protein targeting to the plasma membrane. In this article we report that the exocyst may also play a role in modulating microtubule dynamics. Using monoclonal antibodies, we observed that endogenous exocyst subunits co-localized with microtubules and mitotic spindles in normal rat kidney cells. To test for a functional relationship between the exocyst complex and microtubules, we established an in vitro exocyst reconstitution assay and studied exocyst effect on microtubule dynamics. We found that the exocyst complex reconstituted from eight recombinant exocyst subunits inhibited tubulin polymerization in vitro. Deletion of exocyst subunit sec5, sec6, sec15, or exo70 diminished its tubulin polymerization inhibition activity. Surprisingly, exocyst subunit exo70 itself was also capable of inhibiting tubulin polymerization, although exocyst complex with exo70 deletion did not lose its activity completely. Overexpression of exo70 in NRK cells resulted in microtubule network disruption and the formation of filopodia-like plasma membrane protrusions. The formation of these membrane protrusions was greatly hampered by stabilizing microtubules with taxol. Overexpression of exo84, an exocyst subunit that did not show tubulin polymerization inhibition activity, did not cause this phenotype. Results shown in this article, along with a previous report that localized microtubule instability induces plasma membrane addition, implicates a novel role for the exocyst in modulating microtubule dynamics underlying exocytosis.

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NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex

Cited by 290 publications

References 45 publications

Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals

Changes in NMDA receptor subunits and interacting PSD proteins in dorsolateral prefrontal and anterior cingulate cortex indicate abnormal regional expression in schizophrenia

The Mammalian Exocyst, a Complex Required for Exocytosis, Inhibits Tubulin Polymerization

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