title: Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa.
abstract: Septins are polymerizing GTP binding proteins required for cortical organization during cytokinesis and other cellular processes. A mammalian septin gene Sept4 is expressed mainly in postmitotic neural cells and postmeiotic male germ cells. In mouse and human spermatozoa, SEPT4 and other septins are found in the annulus, a cortical ring which separates the middle and principal pieces. Sept4-/- male mice are sterile due to defective morphology and motility of the sperm flagellum. In Sept4 null spermatozoa, the annulus is replaced by a fragile segment lacking cortical material, beneath which kinesin-mediated intraflagellar transport stalls. The sterility is rescued by injection of sperm into oocytes, demonstrating that each Sept4 null spermatozoon carries an intact haploid genome. The annulus/septin ring is also disorganized in spermatozoa from a subset of human patients with asthenospermia syndrome. Thus, cortical organization based on circular assembly of the septin cytoskeleton is essential for the structural and mechanical integrity of mammalian spermatozoa.
authors.affiliation: Biochemistry and Cell Biology Unit, HMRO, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ihara
authors.forename: Ayae
authors.initials: A
authors.lastname: Kinoshita
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Ai
authors.initials: A
authors.lastname: Tanigaki
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kitano
authors.forename: Motohito
authors.initials: M
authors.lastname: Goto
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Okubo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishiyama
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
authors.forename: Chiaki
authors.initials: C
authors.lastname: Takahashi
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Itohara
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Nishimune
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
authors.forename: Makoto
authors.initials: M
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D058112:Septins; D013094:Spermatozoa / Q000378:metabolism / Q000648:ultrastructure*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D020558:GTP Phosphohydrolases; C115474:Sept4 protein, mouse; D058112:Septins