title: Neuronal P2X2 receptors are mobile ATP sensors that explore the plasma membrane when activated.
abstract: ATP-gated ionotropic P2X2 receptors are widely expressed in neurons. Although the electrophysiological properties of P2X2 receptors have been extensively studied, little is known about the plasma membrane lateral mobility of P2X2 receptors or whether receptor mobility is regulated by ATP. Here we used single-molecule imaging with simultaneous whole-cell voltage-clamp recordings to track quantum dot-labeled P2X2 receptors in the dendrites of rat hippocampal neurons to explore P2X2 receptor mobility and its regulation. We find that plasma membrane P2X2 receptor lateral mobility in dendrites is heterogeneous but mostly Brownian in nature, consisting of mobile and slowly mobile receptor pools. Moreover, lateral mobility is P2X2 subunit and cell specific, is increased in an activation-dependent manner, and is regulated by cytosolic VILIP1, a calcium binding protein. Our data provide the first direct measures of P2X receptor mobility and show that P2X2 receptors are mobile ATP sensors, sampling more of the dendritic plasma membrane in response to ATP.
authors.affiliation: Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Richler
authors.forename: Eiji
authors.initials: E
authors.lastname: Shigetomi
authors.forename: Baljit S
authors.initials: BS
authors.lastname: Khakh
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D051596:Neurocalcin / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection / Q000379:methods
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D051596:Neurocalcin; D018048:Receptors, Purinergic P2; C496688:VSNL1 protein, human; C054562:yellow fluorescent protein, Bacteria; D000255:Adenosine Triphosphate; D002118:Calcium
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