title: N-wasp is required for structural integrity of the blood-testis barrier.
abstract: During spermatogenesis, the blood-testis barrier (BTB) segregates the adluminal (apical) and basal compartments in the seminiferous epithelium, thereby creating a privileged adluminal environment that allows post-meiotic spermatid development to proceed without interference of the host immune system. A key feature of the BTB is its continuous remodeling within the Sertoli cells, the major somatic component of the seminiferous epithelium. This remodeling is necessary to allow the transport of germ cells towards the seminiferous tubule interior, while maintaining intact barrier properties. Here we demonstrate that the actin nucleation promoting factor Neuronal Wiskott-Aldrich Syndrome Protein (N-WASP) provides an essential function necessary for BTB restructuring, and for maintaining spermatogenesis. Our data suggests that the N-WASP-Arp2/3 actin polymerization machinery generates branched-actin arrays at an advanced stage of BTB remodeling. These arrays are proposed to mediate the restructuring process through endocytic recycling of BTB components. Disruption of N-WASP in Sertoli cells results in major structural abnormalities to the BTB, including mis-localization of critical junctional and cytoskeletal elements, and leads to disruption of barrier function. These impairments result in a complete arrest of spermatogenesis, underscoring the critical involvement of the somatic compartment of the seminiferous tubules in germ cell maturation.
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors: Xiang
authors: X
authors: Xiao
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors: Dolores D
authors: DD
authors: Mruk
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors: Elizabeth I
authors: EI
authors: Tang
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors: R'ada
authors: R
authors: Massarwa
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors: Ka Wai
authors: KW
authors: Mok
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors: Nan
authors: N
authors: Li
authors: Department of Biology, Hong Kong Baptist University, Hong Kong, China.
authors: Chris K C
authors: CK
authors: Wong
authors: School of Biological Sciences, University of Hong Kong, Hong Kong, China.
authors: Will M
authors: WM
authors: Lee
authors: Harvard Medical School, Boston, Massachusetts, United States of America.
authors: Scott B
authors: SB
authors: Snapper
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors: Ben-Zion
authors: BZ
authors: Shilo
authors: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
authors: Eyal D
authors: ED
authors: Schejter
authors: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, United States of America.
authors: C Yan
authors: CY
authors: Cheng
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics* / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001814:Blood-Testis Barrier; D008297:Male; D051379:Mice; D012670:Seminiferous Epithelium / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism; D013090:Spermatocytes / Q000254:growth & development / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal