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 hippo- campal 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 regu- late 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 mech- anism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intel- lectual disability.

The X-Linked Intellectual Disability Protein TSPAN7 Regulates Excitatory Synapse Development and AMPAR Trafficking

Cingolani L;
2012-01-01

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 hippo- campal 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 regu- late 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 mech- anism for the functional maturation of glutamatergic synapses, whose impairment is implicated in intel- lectual disability.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2938966
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