An essential role for katanin p80 and microtubule severing in male gamete production.
Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics. Katanin consists of a p60 severing enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate complex targeting and severing activity, but its precise role remains elusive. In lower-order species, the katanin complex has been shown to modulate mitotic and female meiotic spindle dynamics and flagella development. The in vivo function of katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for male fertility. Specifically, through an analysis of a mouse loss-of-function allele (the Taily line), we demonstrate that katanin p80, most likely in association with p60, has an essential role in male meiotic spindle assembly and dissolution and the removal of midbody microtubules and, thus, cytokinesis. Katanin p80 also controls the formation, function, and dissolution of a microtubule structure intimately involved in defining sperm head shaping and sperm tail formation, the manchette, and plays a role in the formation of axoneme microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse, results in male sterility characterized by decreased sperm production, sperm with abnormal head shape, and a virtual absence of progressive motility. Collectively these data demonstrate that katanin p80 serves an essential and evolutionarily conserved role in several aspects of male germ cell development.
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Liza
L
O'Donnell
Danielle
D
Rhodes
Stephanie J
SJ
Smith
D Jo
DJ
Merriner
Brett J
BJ
Clark
Claire
C
Borg
Belinda
B
Whittle
Anne E
AE
O'Connor
Lee B
LB
Smith
Francis J
FJ
McNally
David M
DM
de Kretser
Chris C
CC
Goodnow
Chris J
CJ
Ormandy
Duangporn
D
Jamsai
Moira K
MK
O'Bryan
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D053627:Asthenozoospermia / Q000235:genetics; D015870:Gene Expression; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics*; D000074201:Katanin; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D008870:Microtubules / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009845:Oligospermia / Q000235:genetics; D021122:Protein Subunits / Q000235:genetics; D013081:Sperm Motility / Q000235:genetics; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008941:Spindle Apparatus / Q000235:genetics; D013737:Testis / Q000378:metabolism
D021122:Protein Subunits; D000251:Adenosine Triphosphatases; D000074201:Katanin