The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis.
The Arf GAP SMAP2 is necessary for organized vesicle budding from the trans-Golgi network and subsequent acrosome formation in spermiogenesis.
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DOI：
10.1091/mbc.e13-05-0234
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发表时间：
2013-09
影响因子：
3.3
通讯作者：
Satake M
中科院分区：
文献类型：
--
作者：
Funaki T;Kon S;Tanabe K;Natsume W;Sato S;Shimizu T;Yoshida N;Wong WF;Ogura A;Ogawa T;Inoue K;Ogonuki N;Miki H;Mochida K;Endoh K;Yomogida K;Fukumoto M;Horai R;Iwakura Y;Ito C;Toshimori K;Watanabe T;Satake M
SMAP 2是Arf GAP，并调节网格蛋白包被的囊泡形成。SMAP 2缺陷的雄性小鼠表现出由于顶体变形的球形精子症。在SMAP 2（−/−）精子细胞中，TGN的前顶体囊泡出芽被扭曲，网格蛋白运输相关分子如CALM和突触融合蛋白2被错误定位。反式高尔基体网络（trans-Golgi network，TGN）在网格蛋白包被的膜囊泡的胞吐作用中充当枢纽细胞器，并且SMAP 2是结合网格蛋白和网格蛋白组装蛋白（CALM）的Arf GTP酶激活蛋白。在本研究中，SMAP 2在粗线期精母细胞到精子发生的圆形精子细胞阶段的TGN上被检测到。基因靶向研究表明，SMAP 2缺陷的雄性小鼠是健康的，可以存活到成年，但不育并表现出球形精子症。在SMAP 2缺陷型精子细胞中，从TGN出芽的原顶体囊泡直径增加，TGN结构扭曲，顶体形成严重受损，细胞核重组不能正常进行。CALM的功能是调节囊泡的大小，这项研究表明，CALM不会招募到TGN在SMAP 2的情况下。此外，突触融合蛋白2，可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）复合物的一个组成部分，没有适当地集中在顶体形成的网站。因此，这项研究揭示了SMAP 2和CALM/突触融合蛋白2之间的联系，网格蛋白包被的囊泡形成从TGN和随后的顶体形成。SMAP 2缺陷小鼠提供了人类球形精子症的模型。
SMAP2 is an Arf GAP and modulates clathrin-coated vesicle formation. SMAP2-deficient male mice exhibited globozoospermia due to acrosome deformation. In SMAP2(−/−) spermatids, budding of proacrosomal vesicles from the TGN was distorted and clathrin traffic–related molecules such as CALM and syntaxin2 were mislocated. 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.