title: Ca(2+) influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites.
abstract: In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca(2+) imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca(2+) increase, following cofilin rods' formation. ATP-induced cofilin rods' formation was not observed in cells expressing unphosphorylatable variant of cofilin. A P2X receptor agonist, but not P2Y, induced the formation of cofilin rods, whereas calmodulin and calcineurin inhibitors suppressed it. These results indicate that Ca(2+) influx through P2X receptors induces the formation of cofilin rods via calcineurin-dependent dephosphorylation of cofilin. This pathway might be one candidate to explain the effects of ATP on neuronal development and injury.
authors.affiliation: Center for Biosciences and Informatics, School of Fundamental Science and Technology, Graduate School of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa 223-8522, Japan. homma@cdb.riken.jp
authors.forename: Kohei
authors.initials: K
authors.lastname: Homma
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Niino
authors.forename: Kohji
authors.initials: K
authors.lastname: Hotta
authors.forename: Kotaro
authors.initials: K
authors.lastname: Oka
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000199:Actins / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D051338:Cofilin 1 / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D005455:Fluorescent Antibody Technique; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000199:Actins; D065095:Calcineurin Inhibitors; C495812:Cfl1 protein, rat; D051338:Cofilin 1; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate; D019703:Calcineurin; D002118:Calcium