Filamin A is required for spindle migration and asymmetric division in mouse oocytes

FASEB J. 2017 Aug;31(8):3677-3688. doi: 10.1096/fj.201700056R. Epub 2017 May 9.

Abstract

Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels. Moreover, FLNA knockdown reduced the phosphorylation of cofilin and Rho kinase (ROCK) near the spindle. Similar phenotypes, such as decreased filament actin levels, impaired spindle migration and polar body extrusion, were observed when active cofilin (S3A) was overexpressed or ROCK was inhibited. Notably, we found that FLNA and ROCK interacted directly in mouse oocytes. Taken together, our results show that FLNA plays crucial roles in asymmetric division during meiotic maturation by regulating ROCK-cofilin-mediated actin reorganization.-Wang, H., Guo J., Lin, Z., Namgoong, S., Oh, J. S., Kim, N.-H. Filamin A is required for spindle migration and asymmetric division in mouse oocytes.

Keywords: FLNA; ROCK; actin; cofilin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism
  • Animals
  • Cell Division / physiology*
  • Cloning, Molecular
  • Cytoplasm / chemistry
  • Female
  • Filamins / genetics
  • Filamins / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • Gene Knockdown Techniques
  • Mice
  • Oocytes / cytology
  • Oocytes / physiology*
  • Protein Transport
  • Spindle Apparatus / physiology*
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Filamins
  • rho-Associated Kinases