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Article Dans Une Revue PLoS ONE Année : 2012

A Dual Polybasic Motif Determines Phosphoinositide Binding and Regulation in the P2X Channel Family

Résumé

Phosphoinositides modulate the function of several ion channels, including most ATP-gated P2X receptor channels in neurons and glia, but little is known about the underlying molecular mechanism. We identified a phosphoinositide-binding motif formed of two clusters of positively charged amino acids located on the P2X cytosolic C-terminal domain, proximal to the second transmembrane domain. For all known P2X subtypes, the specific arrangement of basic residues in these semi-conserved clusters determines their sensitivity to membrane phospholipids. Neutralization of these positive charges disrupts the functional properties of the prototypical phosphoinositide-binding P2X4 subtype, mimicking wortmannin-induced phosphoinositide depletion, whereas adding basic residues at homologous positions to the natively insensitive P2X5 subtype establishes de novo phosphoinositide-mediated regulation. Moreover, biochemical evidence of in vitro P2X subunit-phospholipid interaction and functional intracellular phosphoinositide-binding assays demonstrate that the dual polybasic cluster is necessary and sufficient for regulation of P2X signaling by phospholipids.

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Neurobiologie
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hal-01146617 , version 1 (28-04-2015)

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Louis-Philippe Bernier, Dominique Blais, Eric Boué-Grabot, Philippe Séguéla. A Dual Polybasic Motif Determines Phosphoinositide Binding and Regulation in the P2X Channel Family. PLoS ONE, 2012, 7 (7), p.e0040595. ⟨10.1371/journal.pone.0040595⟩. ⟨hal-01146617⟩

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