Nectin couples cell-cell adhesion and the actin scaffold at heterotypic testicular junctions.
Actin-based cell-cell adherens junctions (AJs) are crucial not only for mechanical adhesion but also for cell morphogenesis and differentiation. 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. Recently, nectin-2 (-/-) mice have been shown to exhibit the defective sperm morphogenesis and the male-specific infertility, 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 nectin with the actin cytoskeleton, 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.
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, 2-2 Yamada-oka, Japan.
Kumi
K
Ozaki-Kuroda
Hiroyuki
H
Nakanishi
Hiroshi
H
Ohta
Hiromitsu
H
Tanaka
Hidetake
H
Kurihara
Steffen
S
Mueller
Kenji
K
Irie
Wataru
W
Ikeda
Tatsuo
T
Sakai
Eckard
E
Wimmer
Yoshitake
Y
Nishimune
Yoshimi
Y
Takai
D000199:Actins / Q000378:metabolism*; D022005:Adherens Junctions / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D009218:Myosins; D000075983:Nectins; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013087:Spermatids / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013737:Testis / Q000166:cytology
D000199:Actins; C490657:Afdn protein, mouse; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; C000619017:Nectin3 protein, mouse; D000075983:Nectins; C108835:afadin; D009218:Myosins; D016547:Kinesins