title: An autocrine axis in the testis that coordinates spermiation and blood-testis barrier restructuring during spermatogenesis.
abstract: The mechanism(s) that regulate and coordinate the events of spermiation and blood-testis barrier (BTB) restructuring in the seminiferous epithelium that occur concurrently at stage VIII of the seminiferous epithelial cycle of spermatogenesis are unknown. In this report, fragments derived from the laminin complex composed of laminin alpha3, beta3, and gamma3 chains (laminin-333) at the apical ectoplasmic specialization (apical ES) were shown to modulate BTB dynamics directly and/or indirectly via hemidesmosome. Experiments were performed using cultured Sertoli cells with functional tight junction (TJ) barrier and the ultrastructural features of the BTB but not apical ES. Recombinant protein fragments of laminin beta3 and gamma3 chains were shown to reduce the protein levels of occludin and beta1-integrin dose dependently at the Sertoli-Sertoli and Sertoli-basement membrane interface, respectively, thereby destabilizing the BTB permeability function. These results were corroborated by transient overexpression of laminin fragments in Sertoli cells. To further assess the role of beta1-integrin in hemidesmosome, knockdown of beta1-integrin in Sertoli cells by RNAi was found to associate with occludin redistribution at the Sertoli-Sertoli cell interface, wherein occludin moved away from the cell surface and became associated with endosomes, thereby destabilizing the BTB. In short, an apical ES-BTB-hemidesmosome autocrine regulatory axis was identified in testes, coordinating the events of spermiation and BTB restructuring that occur at the opposite ends of the seminiferous epithelium during spermatogenesis.
authors.affiliation: Center for Biomedical Research, Population Council, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Helen H N
authors.initials: HH
authors.lastname: Yan
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
authors.forename: Elissa W P
authors.initials: EW
authors.lastname: Wong
authors.forename: Will M
authors.initials: WM
authors.lastname: Lee
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D001814:Blood-Testis Barrier / Q000378:metabolism*; D002478:Cells, Cultured; D019012:Integrin beta1 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D062793:Occludin; D010446:Peptide Fragments / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000166:cytology / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D019012:Integrin beta1; D007797:Laminin; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010446:Peptide Fragments