Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

A family of microtubule-severing proteins required for male fertility (#78)

Liza O'Donnell 1 2 , Danielle Rhodes 3 , Jessica E.M. Dunleavy 3 , D. Jo Merriner 3 , Anne E. O'Connor 3 , Lee B. Smith 4 , Duangporn Jamsai 1 , Moira O'Bryan 1
  1. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
  2. MIMR-PHI Institute, Clayton, VIC, Australia
  3. Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia
  4. MRC Centre for Reproductive Health, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom

Microtubules are the building blocks of many cellular structures, and their precise regulation is essential for cell division, function and survival. Microtubule severing enzymes cut, or sever, microtubules and control microtubule dynamics, number and length. Katanin, discovered in sea urchins, is the best characterised microtubule severing complex, consisting of a severing enzyme subunit (p60) and a regulatory subunit (p80). The p60-p80 katanin complex regulates multiple aspects of microtubule dynamics, and is particularly important for mitotic and meiotic spindle assembly and function in lower order species. Mammals express a family of katanin proteins, including p60, p80 and two p60-like proteins KATNAL1 and KATNAL2. In a research program aimed at identifying genes essential for male fertility, we discovered that katanin is essential for sperm production in mice. Point mutations in three katanin genes (Katnb1 (p80), Katnal1 and Katnal2) cause male sterility in the absence of other overt pathological abnormalities, and each regulate particular aspects of sperm development. Using a range of mouse models to define the roles of katanin proteins in mammalian biology, we have shown that p80 katanin is required for the assembly of a normal meiotic spindle, and that successful completion of male meiotic division is dose-dependently sensitive to a loss of p80 protein. We have also shown that a novel severing enzyme, KATNAL2, is present in many ciliated organisms and is required for the assembly of the microtubule-based axoneme core of sperm flagella in mice. Both p80 and KATNAL2 regulate manchette function and sperm head shaping. KATNAL2 exists as several proteins, generated from alternative splicing, which are likely to exhibit functional differences. Our research suggests that multiple proteins contribute to katanin action in mammals, and that each of these proteins have specific roles in male gametogenesis.