title: The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis.
abstract: The trans-Golgi network (TGN) functions as a hub organelle in the exocytosis of clathrin-coated membrane vesicles, and SMAP2 is an Arf GTPase-activating protein that binds to both clathrin and the clathrin assembly protein (CALM). In the present study, SMAP2 is detected on the TGN in the pachytene spermatocyte to the round spermatid stages of spermatogenesis. Gene targeting reveals that SMAP2-deficient male mice are healthy and survive to adulthood but are infertile and exhibit globozoospermia. In SMAP2-deficient spermatids, the diameter of proacrosomal vesicles budding from TGN increases, TGN structures are distorted, acrosome formation is severely impaired, and reorganization of the nucleus does not proceed properly. CALM functions to regulate vesicle sizes, and this study shows that CALM is not recruited to the TGN in the absence of SMAP2. Furthermore, syntaxin2, a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, is not properly concentrated at the site of acrosome formation. Thus this study reveals a link between SMAP2 and CALM/syntaxin2 in clathrin-coated vesicle formation from the TGN and subsequent acrosome formation. SMAP2-deficient mice provide a model for globozoospermia in humans.
authors.affiliation: Department of Molecular Immunology, Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
authors.forename: Tomo
authors.initials: T
authors.lastname: Funaki
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kon
authors.forename: Kenji
authors.initials: K
authors.lastname: Tanabe
authors.forename: Waka
authors.initials: W
authors.lastname: Natsume
authors.forename: Sayaka
authors.initials: S
authors.lastname: Sato
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Naomi
authors.initials: N
authors.lastname: Yoshida
authors.forename: Won Fen
authors.initials: WF
authors.lastname: Wong
authors.forename: Atsuo
authors.initials: A
authors.lastname: Ogura
authors.forename: Takehiko
authors.initials: T
authors.lastname: Ogawa
authors.forename: Kimiko
authors.initials: K
authors.lastname: Inoue
authors.forename: Narumi
authors.initials: N
authors.lastname: Ogonuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Miki
authors.forename: Keiji
authors.initials: K
authors.lastname: Mochida
authors.forename: Keisuke
authors.initials: K
authors.lastname: Endoh
authors.forename: Kentarou
authors.initials: K
authors.lastname: Yomogida
authors.forename: Manabu
authors.initials: M
authors.lastname: Fukumoto
authors.forename: Reiko
authors.initials: R
authors.lastname: Horai
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Chizuru
authors.initials: C
authors.lastname: Ito
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Toshimori
authors.forename: Toshio
authors.initials: T
authors.lastname: Watanabe
authors.forename: Masanobu
authors.initials: M
authors.lastname: Satake
mesh_terms: D000177:Acrosome / Q000378:metabolism*; D000818:Animals; D002966:Clathrin / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D034041:Monomeric Clathrin Assembly Proteins / Q000235:genetics / Q000378:metabolism*; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis; D050827:Syntaxin 1 / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D002966:Clathrin; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; C573094:PICALM protein, mouse; C529588:SMAP2 protein, mouse; D050827:Syntaxin 1