title: A role for sphingomyelin-rich lipid domains in the accumulation of phosphatidylinositol-4,5-bisphosphate to the cleavage furrow during cytokinesis.
abstract: Cytokinesis is a crucial step in the creation of two daughter cells by the formation and ingression of the cleavage furrow. Here, we show that sphingomyelin (SM), one of the major sphingolipids in mammalian cells, is required for the localization of phosphatidylinositol-4,5-bisphosphate (PIP(2)) to the cleavage furrow during cytokinesis. Real-time observation with a labeled SM-specific protein, lysenin, revealed that SM is concentrated in the outer leaflet of the furrow at the time of cytokinesis. Superresolution fluorescence microscopy analysis indicates a transbilayer colocalization between the SM-rich domains in the outer leaflet and PIP(2)-rich domains in the inner leaflet of the plasma membrane. The depletion of SM disperses PIP(2) and inhibits the recruitment of the small GTPase RhoA to the cleavage furrow, leading to abnormal cytokinesis. These results suggest that the formation of SM-rich domains is required for the accumulation of PIP(2) to the cleavage furrow, which is a prerequisite for the proper translocation of RhoA and the progression of cytokinesis.
authors.affiliation: Lipid Biology Laboratory, RIKEN Advanced Science Institute, Wako, Saitama, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Abe
authors.forename: Asami
authors.initials: A
authors.lastname: Makino
authors.forename: Françoise
authors.initials: F
authors.lastname: Hullin-Matsuda
authors.forename: Keiju
authors.initials: K
authors.lastname: Kamijo
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ohno-Iwashita
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hanada
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mizuno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D021381:Protein Transport; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D019269:Phosphatidylinositol 4,5-Diphosphate; D013107:Sphingolipids; D020742:rhoA GTP-Binding Protein