KATNB1 is a master regulator of multiple katanin enzymes in male meiosis and haploid germ cell development

Development. 2021 Dec 15;148(24):dev199922. doi: 10.1242/dev.199922. Epub 2021 Dec 15.

Abstract

Katanin microtubule-severing enzymes are crucial executers of microtubule regulation. Here, we have created an allelic loss-of-function series of the katanin regulatory B-subunit KATNB1 in mice. We reveal that KATNB1 is the master regulator of all katanin enzymatic A-subunits during mammalian spermatogenesis, wherein it is required to maintain katanin A-subunit abundance. Our data shows that complete loss of KATNB1 from germ cells is incompatible with sperm production, and we reveal multiple new spermatogenesis functions for KATNB1, including essential roles in male meiosis, acrosome formation, sperm tail assembly, regulation of both the Sertoli and germ cell cytoskeletons during sperm nuclear remodelling, and maintenance of seminiferous epithelium integrity. Collectively, our findings reveal that katanins are able to differentially regulate almost all key microtubule-based structures during mammalian male germ cell development, through the complexing of one master controller, KATNB1, with a 'toolbox' of neofunctionalised katanin A-subunits.

Keywords: Acrosome; Axoneme; Male fertility; Male infertility; Meiotic spindle; Microtubule severing; Microtubules; Spermiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrosome / metabolism
  • Animals
  • Cytoskeleton / genetics
  • Germ Cells / cytology
  • Germ Cells / growth & development
  • Haploidy*
  • Katanin / genetics*
  • Male
  • Meiosis / genetics*
  • Mice
  • Microtubules / genetics
  • Sertoli Cells / cytology
  • Sperm Tail / metabolism
  • Spermatogenesis / genetics*
  • Spermatozoa / growth & development*
  • Spermatozoa / metabolism

Substances

  • Katnb1 protein, mouse
  • Katanin