title: Dictyostelium huntingtin controls chemotaxis and cytokinesis through the regulation of myosin II phosphorylation.
abstract: Abnormalities in the huntingtin protein (Htt) are associated with Huntington's disease. Despite its importance, the function of Htt is largely unknown. We show that Htt is required for normal chemotaxis and cytokinesis in Dictyostelium discoideum. Cells lacking Htt showed slower migration toward the chemoattractant cAMP and contained lower levels of cortical myosin II, which is likely due to defects in dephosphorylation of myosin II mediated by protein phosphatase 2A (PP2A). htt(-) cells also failed to maintain myosin II in the cortex of the cleavage furrow, generating unseparated daughter cells connected through a thin cytoplasmic bridge. Furthermore, similar to Dictyostelium htt(-) cells, siRNA-mediated knockdown of human HTT also decreased the PP2A activity in HeLa cells. Our data indicate that Htt regulates the phosphorylation status of myosin II during chemotaxis and cytokinesis through PP2A.
authors.affiliation: Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Paul A
authors.initials: PA
authors.lastname: Steimle
authors.forename: Yixin
authors.initials: Y
authors.lastname: Ren
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Robinson
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Egelhoff
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sesaki
authors.forename: Miho
authors.initials: M
authors.lastname: Iijima
mesh_terms: D002455:Cell Division / Q000235:genetics / Q000528:radiation effects; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D015800:Protozoan Proteins; D000242:Cyclic AMP; D054648:Protein Phosphatase 2; D024462:Myosin Type II