Delta tubulin stabilizes male meiotic kinetochores and aids microtubule remodeling and fertility.

Abstract

Delta tubulin (TUBD1) is a noncanonical tubulin protein that has been linked to complex microtubule structures in somatic cell lines and unicellular species. Its role in mammals remains enigmatic; however, TUBD1 is enriched within mammalian male germ cells. Herein, we have defined new roles for TUBD1 during male germ cell development in vivo using a conditional knockout mouse model and shown that spermatogenesis in the absence of TUBD1 causes sterility. We show TUBD1 stabilizes kinetochores during male mouse meiosis, enabling meiotic progression, and that it is required for appropriate spindle polarity and cytokinesis. Subsequently, in haploid cells, TUBD1 works in partnership with the microtubule-severing enzymes KATNAL2 and KATNB1 to regulate manchette remodeling and shape the sperm head. Collectively, these findings reveal TUBD1 plays a key role in the formation and function of highly specialized microtubule structures in mammalian spermatogenesis. Advanced knowledge of TUBD1 may generate new insights into underlying causes of diseases associated with infertility or development.