A Role for Sphingomyelin-Rich Lipid Domains in the Accumulation of Phosphatidylinositol-4,5-Bisphosphate to the Cleavage Furrow during Cytokinesis

Author:

Abe Mitsuhiro1,Makino Asami1,Hullin-Matsuda Françoise12,Kamijo Keiju3,Ohno-Iwashita Yoshiko4,Hanada Kentaro5,Mizuno Hideaki6,Miyawaki Atsushi6,Kobayashi Toshihide12

Affiliation:

1. Lipid Biology Laboratory, RIKEN Advanced Science Institute, Wako, Saitama, Japan

2. INSERM U1060, Université Lyon 1, INSA Lyon, Villeurbanne, France

3. Department of Stem Cell Biology and Histology, Tohoku University School of Medicine, Sendai, Miyagi, Japan

4. Faculty of Pharmacy, Iwaki Meisei University, Iwaki, Fukushima, Japan

5. Department of Biochemistry and Cell Biology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan

6. Laboratory for Cell Function and Dynamics, RIKEN Brain Science Institute, Wako, Saitama, Japan

Abstract

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.

Publisher

American Society for Microbiology

Subject

Cell Biology,Molecular Biology

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