PMID- 26990065 OWN - NLM STAT- MEDLINE DCOM- 20170605 LR - 20181113 IS - 1945-7170 (Electronic) IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 157 IP - 5 DP - 2016 May TI - Planar Cell Polarity (PCP) Protein Vangl2 Regulates Ectoplasmic Specialization Dynamics via Its Effects on Actin Microfilaments in the Testes of Male Rats. PG - 2140-59 LID - 10.1210/en.2015-1987 [doi] AB - Planar cell polarity (PCP) proteins confer polarization of a field of cells (eg, elongating/elongated spermatids) within the plane of an epithelium such as the seminiferous epithelium of the tubule during spermatogenesis. In adult rat testes, Sertoli and germ cells were found to express PCP core proteins (eg, Van Gogh-like 2 [Vangl2]), effectors, ligands, and signaling proteins. Vangl2 expressed predominantly by Sertoli cells was localized at the testis-specific, actin-rich ectoplasmic specialization (ES) at the Sertoli-spermatid interface in the adluminal compartment and also Sertoli-Sertoli interface at the blood-testis barrier (BTB) and structurally interacted with actin, N-cadherin, and another PCP/polarity protein Scribble. Vangl2 knockdown (KD) by RNA interference in Sertoli cells cultured in vitro with an established tight junction-permeability barrier led to BTB tightening, whereas its overexpression using a full-length cDNA construct perturbed the barrier function. These changes were mediated through an alteration on the organization actin microfilaments at the ES in Sertoli cells, involving actin-regulatory proteins, epidermal growth factor receptor pathway substrate 8, actin-related protein 3, and Scribble, which in turn affected the function of adhesion protein complexes at the ES during the epithelial cycle of spermatogenesis. Using Polyplus in vivo-jetPEI reagent as a transfection medium to silence Vangl2 in the testis in vivo by RNA interference with high efficacy, Vangl2 KD led to changes in F-actin organization at the ES in the epithelium, impeding spermatid and phagosome transport and spermatid polarity, meiosis, and BTB dynamics. For instance, step 19 spermatids remained embedded in the epithelium alongside with step 9 and 10 spermatids in stages IX-X tubules. In summary, the PCP protein Vangl2 is an ES regulator through its effects on actin microfilaments in the testis. FAU - Chen, Haiqi AU - Chen H AD - The Mary M. Wohlford Laboratory for Male Contraceptive Research (H.C., D.D.M., C.Y.C.), Center for Biomedical Research, Population Council, New York, New York 10065; and School of Biological Sciences (W.M.L.), University of Hong Kong, Pokfulam, Hong Kong, China. FAU - Mruk, Dolores D AU - Mruk DD AD - The Mary M. Wohlford Laboratory for Male Contraceptive Research (H.C., D.D.M., C.Y.C.), Center for Biomedical Research, Population Council, New York, New York 10065; and School of Biological Sciences (W.M.L.), University of Hong Kong, Pokfulam, Hong Kong, China. FAU - Lee, Will M AU - Lee WM AD - The Mary M. Wohlford Laboratory for Male Contraceptive Research (H.C., D.D.M., C.Y.C.), Center for Biomedical Research, Population Council, New York, New York 10065; and School of Biological Sciences (W.M.L.), University of Hong Kong, Pokfulam, Hong Kong, China. FAU - Cheng, C Yan AU - Cheng CY AD - The Mary M. Wohlford Laboratory for Male Contraceptive Research (H.C., D.D.M., C.Y.C.), Center for Biomedical Research, Population Council, New York, New York 10065; and School of Biological Sciences (W.M.L.), University of Hong Kong, Pokfulam, Hong Kong, China. LA - eng GR - R01 HD056034/HD/NICHD NIH HHS/United States GR - U54 HD029990/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160318 PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Actin-Related Protein 3) RN - 0 (Nerve Tissue Proteins) RN - 0 (Tumor Suppressor Proteins) RN - 0 (Vangl2 protein, rat) RN - 0 (scribble protein, rat) SB - IM MH - Actin Cytoskeleton/*metabolism MH - Actin-Related Protein 3/metabolism MH - Animals MH - Blood-Testis Barrier/*metabolism MH - Cell Polarity/physiology MH - Cells, Cultured MH - Male MH - Nerve Tissue Proteins/genetics/*metabolism MH - RNA Interference MH - Rats MH - Sertoli Cells/cytology/*metabolism MH - Spermatids/cytology/metabolism MH - Spermatogenesis/physiology MH - Testis/cytology/*metabolism MH - Tumor Suppressor Proteins/metabolism PMC - PMC4870864 EDAT- 2016/03/19 06:00 MHDA- 2017/06/06 06:00 PMCR- 2017/05/01 CRDT- 2016/03/19 06:00 PHST- 2016/03/19 06:00 [entrez] PHST- 2016/03/19 06:00 [pubmed] PHST- 2017/06/06 06:00 [medline] PHST- 2017/05/01 00:00 [pmc-release] AID - EN-15-1987 [pii] AID - 10.1210/en.2015-1987 [doi] PST - ppublish SO - Endocrinology. 2016 May;157(5):2140-59. doi: 10.1210/en.2015-1987. Epub 2016 Mar 18.