Typically, KATNA1 binding to KATNB1 enhances severing, likely due to KATNB1 increasing the stability of the KATNA1 hexamer. In its active ATP-bound state, KATNA1 forms hexameric rings capable of binding to and severing microtubule polymers. Since then, the KATNA1-KATNB1 complex has emerged as a critical regulator of microtubule dynamics in a range of contexts, including mitosis, cilia biogenesis and disassembly, neurogenesis and cell migration. The katanins are members of the ATPases Associated with diverse cellular Activities (AAA) superfamily, and were first identified via the microtubule severing activity of the catalytic KATNA1 (p60) and its regulatory protein, KATNB1 (p80), and their pivotal roles in defining meiotic spindle structure in Caenorhabditis elegans. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared no competing interests exist. MB received was funded by the Deutsche Forschungsgemeinschaft (DFG), as part of an International Research Training Group project. JEMD was the recipient of an Australian Government Research Training Program Scholarship. HO was funded by Japan Society for the Promotion of Science Research Fellowship for Young Scientists. MKO is the recipient of a National Health and Medical Research Council Fellowship (APP1058356). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: All relevant data are within the paper and its Supporting Information files.įunding: The project was funded by an Australian Research Council of Australia Discovery Grant to MKO (DP160100647). Received: ApAccepted: OctoPublished: November 14, 2017Ĭopyright: © 2017 Dunleavy et al. Matzuk, Baylor College of Medicine, UNITED STATES (2017) Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse. Our research has immediate relevance to the origins of human male infertility and provides novel insights into aspects of microtubule regulation relevant to numerous tissues and species.Ĭitation: Dunleavy JEM, Okuda H, O’Connor AE, Merriner DJ, O’Donnell L, Jamsai D, et al. Further, we show for the first time, that KATNAL2 can function both independently or in concert with the katanin regulatory protein KATNB1 and that it can target the poorly characterized tubulin subunits delta and epsilon. Notably, we show the function of microtubule-based structures involved in sperm head shaping and tail formation are disrupted. We show that mice with compromised KATNAL2 function are male sterile as a consequence of defects in the structural remodelling of germ cells. Within this manuscript, we have used spermatogenesis to define the function of the putative microtubule-severing protein katanin-like 2 (KATNAL2). The precise regulation of microtubule number, length and movement is thus, essential for male fertility. Microtubules are cellular “scaffolds” that serve critical roles in all cells, including developing male germ cells wherein they facilitate mitosis and meiosis (cell division), sperm head remodelling and sperm tail formation. Despite this, the biochemical basis of common defects, including reduced sperm count and abnormal sperm structure and function, remains poorly defined. Male infertility affects one in twenty men of reproductive age in western countries. Together with our previous research, showing the essential requirement of katanin proteins KATNAL1 and KATNB1 during spermatogenesis, our data supports the concept that in higher order species the presence of multiple katanins has allowed for subspecialisation of function within complex cellular settings such as the seminiferous epithelium. Moreover, our data indicate KATNAL2 may regulate δ- and ε-tubulin rather than classical α-β-tubulin microtubule polymers, suggesting the katanin family has a greater diversity of function than previously realised. We present data suggesting that depending on context, KATNAL2 can partner with the regulatory protein KATNB1 or act autonomously. Here we have defined critical roles for the poorly characterised katanin protein KATNAL2 in multiple aspects of spermatogenesis: the initiation of sperm tail growth from the basal body, sperm head shaping via the manchette, acrosome attachment, and ultimately sperm release. The katanin microtubule-severing proteins are essential regulators of microtubule dynamics in a diverse range of species.
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