title: Fascin 1 is an actin filament-bundling protein that regulates ectoplasmic specialization dynamics in the rat testis.
abstract: In the testis, spermatids are polarized cells, with their heads pointing toward the basement membrane during maturation. This polarity is crucial to pack the maximal number of spermatids in the seminiferous epithelium so that millions of sperms can be produced daily. A loss of spermatid polarity is detected after rodents are exposed to toxicants (e.g., cadmium) or nonhormonal male contraceptives (e.g., adjudin), which is associated with a disruption on the expression and/or localization of polarity proteins. In the rat testis, fascin 1, an actin-bundling protein found in mammalian cells, was expressed by Sertoli and germ cells. Fascin 1 was a component of the ectoplasmic specialization (ES), a testis-specific anchoring junction known to confer spermatid adhesion and polarity. Its expression in the seminiferous epithelium was stage specific. Fascin 1 was localized to the basal ES at the Sertoli cell-cell interface of the blood-testis barrier in all stages of the epithelial cycle, except it diminished considerably at late stage VIII. Fascin 1 was highly expressed at the apical ES at stage VII-early stage VIII and restricted to the step 19 spermatids. Its knockdown by RNAi that silenced fascin 1 by ~70% in Sertoli cells cultured in vitro was found to perturb the tight junction-permeability barrier via a disruption of F-actin organization. Knockdown of fascin 1 in vivo by ~60-70% induced defects in spermatid polarity, which was mediated by a mislocalization and/or downregulation of actin-bundling proteins Eps8 and palladin, thereby impeding F-actin organization and disrupting spermatid polarity. In summary, these findings provide insightful information on spermatid polarity regulation.
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York; and.
authors.forename: N Ece
authors.initials: NE
authors.lastname: Gungor-Ordueri
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey.
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.affiliation: The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York; and Y-Cheng@popcbr.rockefeller.edu.
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D001814:Blood-Testis Barrier / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016764:Cell Polarity / Q000187:drug effects; D002478:Cells, Cultured; D003272:Contraceptive Agents, Male / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020868:Gene Silencing; D006834:Hydrazines / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D034741:RNA, Small Interfering; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013087:Spermatids / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C432482:1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide; D048868:Adaptor Proteins, Signal Transducing; D003272:Contraceptive Agents, Male; C498142:Eps8 protein, rat; C535054:Fscn1 protein, rat; D006834:Hydrazines; D007191:Indazoles; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C000595529:Pald1 protein, rat; D010749:Phosphoprotein Phosphatases
keywords: F-actin; blood-testis barrier; ectoplasmic specialization; fascin 1; seminiferous epithelial cycle; spermatid polarity; spermatogenesis; testis