Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/96268
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Type: Journal article
Title: RAB-like 2 has an essential role in male fertility, sperm intra-flagellar transport, and tail assembly
Author: Lo, J.
Jamsai, D.
O'Connor, A.
Borg, C.
Clark, B.
Whisstock, J.
Field, M.
Adams, V.
Ishikawa, T.
Aitken, R.
Whittle, B.
Goodnow, C.
Ormandy, C.
O'Bryan, M.
Citation: PLoS Genetics, 2012; 8(10):e1002969-1-e1002969-11
Publisher: Public Library of Science
Issue Date: 2012
ISSN: 1553-7390
1553-7404
Editor: Dutcher, S.
Statement of
Responsibility: 
Jennifer C. Y. Lo, Duangporn Jamsai, Anne E. O’Connor, Claire Borg, Brett J. Clark, James C. Whisstock, Mark C. Field, Vicki Adams, Tomomoto Ishikawa, R. John Aitken, Belinda Whittle, Christopher C. Goodnow, Christopher J. Ormandy, Moira K. O’Bryan
Abstract: A significant percentage of young men are infertile and, for the majority, the underlying cause remains unknown. Male infertility is, however, frequently associated with defective sperm motility, wherein the sperm tail is a modified flagella/cilia. Conversely, a greater understanding of essential mechanisms involved in tail formation may offer contraceptive opportunities, or more broadly, therapeutic strategies for global cilia defects. Here we have identified Rab-like 2 (RABL2) as an essential requirement for sperm tail assembly and function. RABL2 is a member of a poorly characterized clade of the RAS GTPase superfamily. RABL2 is highly enriched within developing male germ cells, where it localizes to the mid-piece of the sperm tail. Lesser amounts of Rabl2 mRNA were observed in other tissues containing motile cilia. Using a co-immunoprecipitation approach and RABL2 affinity columns followed by immunochemistry, we demonstrated that within developing haploid germ cells RABL2 interacts with intra-flagella transport (IFT) proteins and delivers a specific set of effector (cargo) proteins, including key members of the glycolytic pathway, to the sperm tail. RABL2 binding to effector proteins is regulated by GTP. Perturbed RABL2 function, as exemplified by the Mot mouse line that contains a mutation in a critical protein-protein interaction domain, results in male sterility characterized by reduced sperm output, and sperm with aberrant motility and short tails. Our data demonstrate a novel function for the RABL protein family, an essential role for RABL2 in male fertility and a previously uncharacterised mechanism for protein delivery to the flagellum.
Keywords: Germ Cells
Rights: © 2012 Lo et al. 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.
DOI: 10.1371/journal.pgen.1002969
Grant ID: http://purl.org/au-research/grants/nhmrc/606445
http://purl.org/au-research/grants/nhmrc/545805
http://purl.org/au-research/grants/nhmrc/481310
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