3 integrin interacts directly with GluA2 AMPA receptor subunit and regulates AMPA receptor expression in hippocampal neurons.

Proc Natl Acad Sci U S A. 2012 Jan 9;
Pozo K, Cingolani LA, Bassani S, Laurent F, Passafaro M, Goda Y

The integrins are transmembrane receptors for ECM proteins, as well as they regulate assorted mobile functions in a central nervous system. In hippocampal neurons, a 3 integrin subtype is required for homeostatic synaptic scaling of AMPA receptors (AMPARs) induced by chronic activity deprivation. The surface level of 3 integrin in postsynaptic neurons directly correlates with synaptic strength as well as a abundance of synaptic GluA2 AMPAR subunit. Although these observations indicate a functional link in between 3 integrin as well as AMPAR, little is known about a mechanistic basement for a connection. Here you investigate a nature of 3 integrin as well as AMPAR interaction underlying a 3 integrin-dependent control of synaptic AMPAR expression as well as thus synaptic strength. We show that 3 integrin as well as GluA2 subunit form a complex in mouse brain that involves a direct contracting in between their cytoplasmic domains. In contrast, 3 integrin associates with GluA1 AMPAR subunit only weakly, and, in a heterologous expression system, a interaction requires a coexpression of GluA2. Surprisingly, in hippocampal pyramidal neurons, expressing 3 integrin mutants with either increased or decreased affinity for extracellular ligands has no differential effects in elevating excitatory synaptic currents as well as surface GluA2 levels compared with WT 3 integrin. Our findings identify an integrin family member, 3, as a direct interactor of an AMPAR subunit as well as yield molecular insights into how this cell-adhesion protein regulates a composition of cell-surface AMPARs.

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