title: AKAP9, a Regulator of Microtubule Dynamics, Contributes to Blood-Testis Barrier Function.
abstract: The blood-testis barrier (BTB), formed between adjacent Sertoli cells, undergoes extensive remodeling to facilitate the transport of preleptotene spermatocytes across the barrier from the basal to apical compartments of the seminiferous tubules for further development and maturation into spermatozoa. The actin cytoskeleton serves unique structural and supporting roles in this process, but little is known about the role of microtubules and their regulators during BTB restructuring. The large isoform of the cAMP-responsive scaffold protein AKAP9 regulates microtubule dynamics and nucleation at the Golgi. We found that conditional deletion of Akap9 in mice after the initial formation of the BTB at puberty leads to infertility. Akap9 deletion results in marked alterations in the organization of microtubules in Sertoli cells and a loss of barrier integrity despite a relatively intact, albeit more apically localized F-actin and BTB tight junctional proteins. These changes are accompanied by a loss of haploid spermatids due to impeded meiosis. The barrier, however, progressively reseals in older Akap9 null mice, which correlates with a reduction in germ cell apoptosis and a greater incidence of meiosis. However, spermiogenesis remains defective, suggesting additional roles for AKAP9 in this process. Together, our data suggest that AKAP9 and, by inference, the regulation of the microtubule network are critical for BTB function and subsequent germ cell development during spermatogenesis.
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Deepak
authors.initials: D
authors.lastname: Venkatesh
authors.affiliation: Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York.
authors.forename: Dolores
authors.initials: D
authors.lastname: Mruk
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jan M
authors.initials: JM
authors.lastname: Herter
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Xavier
authors.initials: X
authors.lastname: Cullere
authors.affiliation: Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Chojnacka
authors.affiliation: Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York.
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: tmayadas@rics.bwh.harvard.edu.
authors.forename: Tanya N
authors.initials: TN
authors.lastname: Mayadas
mesh_terms: D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D001814:Blood-Testis Barrier / Q000378:metabolism*; D005854:Germ Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D012708:Sertoli Cells / Q000166:cytology*; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000378:metabolism*
chemical_list: D054758:A Kinase Anchor Proteins; D000199:Actins; C464931:Akap9 protein, mouse; D008869:Microtubule-Associated Proteins