Regulation of blood-testis barrier dynamics by desmosome, gap junction, hemidesmosome and polarity proteins
Open Access
- 1 April 2011
- journal article
- Published by Taylor & Francis Ltd in Spermatogenesis
- Vol. 1 (2), 105-115
- https://doi.org/10.4161/spmg.1.2.15745
Abstract
The blood-testis barrier (BTB) is a unique ultrastructure in the mammalian testis. Unlike other blood-tissue barriers, such as the blood-brain barrier and the blood-ocular (or blood-retina) barrier which formed by tight junctions (TJ) between endothelial cells of the microvessels, the BTB is constituted by coexisting TJ, basal ectoplasmic specialization (basal ES), desmosomes and gap junctions between adjacent Sertoli cells near the basement membrane of the seminiferous tubule. The BTB also divides the seminiferous epithelium into the apical and basal compartments so that meiosis I and II and post-meiotic germ cell development can all take place in a specialized microenvironment in the apical compartment behind the BTB. While the unusual anatomical features of the BTB have been known for decades, the physiological function of the coexisting junctions, in particular the desmosome and gap junction, that constitute the BTB was unknown until recently. Based on recently published findings, we critically evaluate the role of the desmosome and gap junction that serve as a signaling platform to coordinate the "opening" and "closing" of the TJ-permeability barrier conferred by TJ and basal ES. This is made possible by polarity proteins working in concert with nonreceptor protein tyrosine kinases, such as focal adhesion kinase (FAK) and c-Src, at the site to regulate endosome-mediated protein trafficking events (e.g., endocytosis, transcytosis, recycling, or endosome-mediated protein degradation). These events not only serve to destabilize the existing "old" BTB above preleptotene spermatocytes in transit at the BTB, but also contribute to the assembly of "new" BTB below the transiting spermatocytes. Furthermore, hemidesmosomes at the Sertoli cell-basement membrane interface also contribute to the BTB restructuring events at stage VIII of the epithelial cycle. Additionally, the findings that a gap junction at the BTB provides a possible route for the passage of toxicants [e.g., bisphenol A (BPA)] and potential male contraceptives (e.g., adjudin) across the BTB also illustrate that these coexisting junctions, while helpful to maintain the immunological barrier integrity during the transit of spermatocytes, can be the "gateway" to making the BTB so vulnerable to toxicants and/or chemicals, causing male reproductive dysfunction.Keywords
This publication has 73 references indexed in Scilit:
- Impacts of environmental toxicants on male reproductive dysfunctionTrends in Pharmacological Sciences, 2011
- Differential effects of testosterone and TGF-β3 on endocytic vesicle-mediated protein trafficking events at the blood–testis barrierExperimental Cell Research, 2010
- Crosstalk between desmoglein-2/desmocollin-2/Src kinase and coxsackie and adenovirus receptor/ZO-1 protein complexes, regulates blood-testis barrier dynamicsThe International Journal of Biochemistry & Cell Biology, 2010
- Regulation of spermatogenesis in the microenvironment of the seminiferous epithelium: New insights and advancesMolecular and Cellular Endocrinology, 2010
- Disruption of the blood-testis barrier integrity by bisphenol A in vitro: Is this a suitable model for studying blood-testis barrier dynamics?The International Journal of Biochemistry & Cell Biology, 2009
- TGF-β3 and TNFα perturb blood–testis barrier (BTB) dynamics by accelerating the clathrin-mediated endocytosis of integral membrane proteins: A new concept of BTB regulation during spermatogenesisDevelopmental Biology, 2009
- The PAR Proteins: Fundamental Players in Animal Cell PolarizationDevelopmental Cell, 2007
- Connexin channel permeability to cytoplasmic moleculesProgress in Biophysics and Molecular Biology, 2007
- Coxsackie and adenovirus receptor (CAR) is a product of Sertoli and germ cells in rat testes which is localized at the Sertoli–Sertoli and Sertoli–germ cell interfaceExperimental Cell Research, 2007
- AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMRJournal of Biomolecular NMR, 1996