mDia1/3 generate cortical F-actin meshwork in Sertoli cells that is continuous with contractile F-actin bundles and indispensable for spermatogenesis and male fertility.

Autor: Satoko Sakamoto, Dean Thumkeo, Hiroshi Ohta, Zhen Zhang, Shuangru Huang, Pakorn Kanchanawong, Takayoshi Fuu, Sadanori Watanabe, Kentaro Shimada, Yoshitaka Fujihara, Shosei Yoshida, Masahito Ikawa, Naoki Watanabe, Mitinori Saitou, Shuh Narumiya
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS Biology, Vol 16, Iss 9, p e2004874 (2018)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.2004874
Popis: Formin is one of the two major classes of actin binding proteins (ABPs) with nucleation and polymerization activity. However, despite advances in our understanding of its biochemical activity, whether and how formins generate specific architecture of the actin cytoskeleton and function in a physiological context in vivo remain largely obscure. It is also unknown how actin filaments generated by formins interact with other ABPs in the cell. Here, we combine genetic manipulation of formins mammalian diaphanous homolog1 (mDia1) and 3 (mDia3) with superresolution microscopy and single-molecule imaging, and show that the formins mDia1 and mDia3 are dominantly expressed in Sertoli cells of mouse seminiferous tubule and together generate a highly dynamic cortical filamentous actin (F-actin) meshwork that is continuous with the contractile actomyosin bundles. Loss of mDia1/3 impaired these F-actin architectures, induced ectopic noncontractile espin1-containing F-actin bundles, and disrupted Sertoli cell-germ cell interaction, resulting in impaired spermatogenesis. These results together demonstrate the previously unsuspected mDia-dependent regulatory mechanism of cortical F-actin that is indispensable for mammalian sperm development and male fertility.
Databáze: Directory of Open Access Journals
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