Article

A role for sphingomyelin-rich lipid domains in the accumulation of phosphatidylinositol-4,5-bisphosphate to the cleavage furrow during cytokinesis.

Lipid Biology Laboratory, RIKEN Advanced Science Institute, Wako, Saitama, Japan.
Molecular and cellular biology (impact factor: 6.06). 02/2012; 32(8):1396-407. DOI:10.1128/MCB.06113-11 pp.1396-407
Source: PubMed

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.

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Keywords

abnormal cytokinesis
 
cleavage furrow
 
cytokinesis
 
daughter cells
 
furrow
 
inhibits
 
inner leaflet
 
localization
 
major sphingolipids
 
mammalian cells
 
outer leaflet
 
PIP(2)-rich domains
 
plasma membrane
 
progression
 
Real-time observation
 
SM-rich domains
 
small GTPase RhoA
 
sphingomyelin
 
Superresolution fluorescence microscopy analysis
 
transbilayer colocalization
 

Mitsuhiro Abe