Nectin couples cell-cell adhesion and the actin scaffold at heterotypic testicular junctions

被引:213
作者
Ozaki-Kuroda, K
Nakanishi, H
Ohta, H
Tanaka, H
Kurihara, H
Mueller, S
Irie, K
Ikeda, W
Sakai, T
Wimmer, E
Nishimune, Y
Takai, Y
机构
[1] Osaka Univ, Grad Sch Med, Dept Mol Biol & Biochem, Fac Med, Suita, Osaka 565, Japan
[2] Osaka Univ, Microbial Dis Res Inst, Dept Sci Lab Anim Experimentat, Suita, Osaka 5650871, Japan
[3] Juntendo Univ, Sch Med, Dept Anat, Bunkyo Ku, Tokyo 1138421, Japan
[4] SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
基金
美国国家卫生研究院; 日本学术振兴会;
关键词
D O I
10.1016/S0960-9822(02)00922-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Actin-based cell-cell adherens junctions (AJs) are crucial not only for mechanical adhesion but also for cell morphogenesis and differentiation [1-4]. While organization of homotypic AJs is attributed mostly to classic cadherins, the adhesive mechanism of heterotypic AJs in more complex tissues remains to be clarified. Nectin, a member of a family of immunoglobulin-like adhesion molecules at various AJs, is a possible organizer of heterotypic AJs because of its unique heterophilic trans-interaction property [5-10]. Recently, nectin-2 (-/-) mice have been shown to exhibit the defective sperm morphogenesis and the male-specific infertility [11], but the role of nectin in testicular AJs has not been investigated. We show here the heterotypic trans-interaction between nectin-2 in Sertoli cells and nectin-3 in spermatids at Sertoli-spermatid junctions (SspJs), heterotypic AJs in testes. Moreover, each nectin-based adhesive membrane domain exhibits one-to-one colocalization with each actin bundle underlying SspJs. Inactivation of the mouse nectin-2 gene causes not only impaired adhesion but also loss of the junctional actin scaffold at SspJs, resulting in aberrant morphogenesis and positioning of spermatids. Localization of afadin, an adaptor protein of nec-tin with the actin cytoskeleton [8, 12], is also nectin-2 dependent at SspJs. These results indicate that the nectin-afadin system plays essential roles in coupling cell-cell adhesion and the cortical actin scaffold at SspJs and in subsequent sperm morphogenesis.
引用
收藏
页码:1145 / 1150
页数:6
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