title: Crosstalk between desmoglein-2/desmocollin-2/Src kinase and coxsackie and adenovirus receptor/ZO-1 protein complexes, regulates blood-testis barrier dynamics.
abstract: Morphological studies in the testis reported the presence of 'desmosome-like' junctions between Sertoli cells at the blood-testis barrier, whose function is also constituted by tight junctions and basal ectoplasmic specializations. Unfortunately, little is known about the role of desmosomes in blood-testis barrier dynamics. This study aims to fill this gap with the functional investigation of two desmosomal cadherins, desmoglein-2 and desmocollin-2, by their specific knockdown in Sertoli cells cultured in vitro. Reminiscent of the blood-testis barrier in vivo, desmosome-like structures were visible by electron microscopy when Sertoli cells were cultured at high density, thereby forming a polarized epithelium with functional cell junctions. At this point, we opted to focus our efforts on desmoglein-2 and desmocollin-2 based on results which illustrated desmosomal mRNAs to be expressed by Sertoli and germ cells, as well as on results which illustrated desmoglein-2 to co-immunoprecipitate with plakoglobin, c-Src and desmocollin-2. Simultaneous knockdown of desmoglein-2 and desmocollin-2 not only led to a reduction in and mislocalization of zonula occludens-1, but also perturbed the localization of c-Src and coxsackie and adenovirus receptor at the cell-cell interface, resulting in disruption of tight junction permeability barrier. We hereby propose a novel regulatory protein complex composed of desmoglein-2, desmocollin-2, c-Src, coxsackie and adenovirus receptor and zonula occludens-1 at the blood-testis barrier.
authors.affiliation: Population Council, Center for Biomedical Research, 1230 York Avenue, New York, NY 10065, United States.
authors.forename: Pearl P Y
authors.initials: PP
authors.lastname: Lie
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.forename: Dolores D
authors.initials: DD
authors.lastname: Mruk
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000378:metabolism* / Q000473:pathology; D002199:Capillary Permeability / Q000235:genetics; D002478:Cells, Cultured; D000090702:Constitutive Androstane Receptor; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism*; D051301:Desmoglein 2 / Q000235:genetics / Q000378:metabolism*; D003896:Desmosomes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D012708:Sertoli Cells / Q000378:metabolism* / Q000473:pathology; D019108:Tight Junctions / Q000473:pathology; D062826:Zonula Occludens-1 Protein; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000090702:Constitutive Androstane Receptor; D051187:Desmocollins; D051301:Desmoglein 2; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D018160:Receptors, Cytoplasmic and Nuclear; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D019061:src-Family Kinases