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PLoS Biol. 2018 Sep 26;16(9):e2004874. doi: 10.1371/journal.pbio.2004874. eCollection 2018 Sep.

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.

Author information

1
Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
2
Department of Drug Discovery Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
3
Department of Anatomy and Cell Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
4
Mechanobiology Institute, National University of Singapore, Singapore.
5
Department of Biomedical Engineering, National University of Singapore, Singapore.
6
Research Institute for Microbial Disease, Osaka University, Osaka, Japan.
7
National Institute for Basic Biology, Okazaki, Japan.
8
Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
9
Laboratory of Single-Molecule Cell Biology, Kyoto University Graduate School of Biostudies, Kyoto, Japan.

Abstract

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.

PMID:
30256801
PMCID:
PMC6175529
DOI:
10.1371/journal.pbio.2004874
[Indexed for MEDLINE]
Free PMC Article

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