Chaumont Severine, Compan Vincent, Toulme Estelle, Richler Esther, Housley Gary D, Rassendren Francois, Khakh Baljit S
Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sci Signal. 2008 Oct 14;1(41):ra8. doi: 10.1126/scisignal.1162329.
Extracellular adenosine triphosphate (ATP) activates P2X receptors, which are involved in diverse physiological functions. Using a proteomic approach, we identified the neuronal calcium sensor VILIP1 as interacting with P2X2 receptors. We found that VILIP1 forms a signaling complex in vitro and in vivo with P2X2 receptors and regulates P2X2 receptor sensitivity to ATP, peak response, surface expression, and diffusion. VILIP1 constitutively binds to P2X2 receptors and displays enhanced interactions in an activation- and calcium-dependent manner owing to exposure of its binding segment in P2X2 receptors. VILIP1-P2X2 interactions are also enhanced in hippocampal neurons during conditions of action potential firing known to trigger P2X2 receptor activation. Our data thus reveal a previously unrecognized function for the neuronal calcium sensor protein VILIP1 and a mechanism for regulation of ATP-dependent P2X receptor signaling by neuronal calcium sensors.
细胞外三磷酸腺苷（ATP）激活P2X受体，该受体参与多种生理功能。我们采用蛋白质组学方法，鉴定出神经元钙传感器VILIP1与P2X2受体相互作用。我们发现，VILIP1在体外和体内与P2X2受体形成信号复合物，并调节P2X2受体对ATP的敏感性、峰值反应、表面表达和扩散。VILIP1持续结合P2X2受体，并因其在P2X2受体中的结合片段暴露而以激活和钙依赖的方式增强相互作用。在已知触发P2X2受体激活的动作电位发放条件下，海马神经元中的VILIP1-P2X2相互作用也增强。因此，我们的数据揭示了神经元钙传感器蛋白VILIP1以前未被认识的功能，以及神经元钙传感器调节ATP依赖的P2X受体信号传导的机制。
