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Neuron. 2012 Mar 22;73(6):1143-58. doi: 10.1016/j.neuron.2012.01.021. Epub 2012 Mar 21.

The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking.

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  • 1CNR Institute of Neuroscience, Department of Medical Pharmacology, University of Milan, Milan 20129, Italy.

Abstract

Mutations in TSPAN7--a member of the tetraspanin protein superfamily--are implicated in some forms of X-linked intellectual disability. Here we show that TSPAN7 overexpression promotes the formation of filopodia and dendritic spines in cultured hippocampal neurons from embryonic rats, whereas TSPAN7 silencing reduces head size and stability of spines and AMPA receptor currents. Via its C terminus, TSPAN7 interacts with the PDZ domain of protein interacting with C kinase 1 (PICK1), to regulate PICK1 and GluR2/3 association and AMPA receptor trafficking. These findings indicate that, in hippocampal neurons, TSPAN7 regulates AMPA receptor trafficking by limiting PICK1 accessibility to AMPA receptors and suggest an additional mechanism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intellectual disability.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22445342
[PubMed - indexed for MEDLINE]
PMCID:
PMC3314997
Free PMC Article

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