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Article: Differential effects of testosterone and TGF-Β3 on endocytic vesicle-mediated protein trafficking events at the blood-testis barrier

TitleDifferential effects of testosterone and TGF-Β3 on endocytic vesicle-mediated protein trafficking events at the blood-testis barrier
Authors
KeywordsBlood-testis barrier
Endosome-mediated protein degradation
Protein endocytosis
Protein recycling
Protein transcytosis
Seminiferous epithelial cycle
Spermatogenesis
Testis
Testosterone
TGF-Β3
Issue Date2010
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcr
Citation
Experimental Cell Research, 2010, v. 316 n. 17, p. 2945-2960 How to Cite?
AbstractThe intricate interaction between protein endocytosis, transcytosis, recycling and endosome- or ubiquitin-mediated protein degradation determines the junction integrity in epithelial cells including Sertoli cells at the blood-testis barrier (BTB). Studies have shown that androgens and cytokines (e.g., TGF-Β3) that are known to promote and disrupt BTB integrity, respectively, accelerate protein endocytosis at the BTB. We hypothesized that testosterone-induced endocytosed proteins are transcytosed and recycled back to the Sertoli cell surface, whereas cytokine-induced endocytosed proteins are degraded so that androgens and cytokines have opposing effects on BTB integrity. Herein, we report that both testosterone and TGF-Β3 induced the steady-state level of clathrin, an endocytic vesicle protein. Testosterone and TGF-Β3 also induced the association between internalized occludin (a BTB integral membrane protein) and clathrin, as well as early endosome antigen-1 (EEA-1). Interestingly, testosterone, but not TGF-Β3, also induced the levels of proteins that regulate protein transcytosis (e.g., caveolin-1) and recycling (e.g., Rab11), and their association with internalized occludin and N-cadherin from the cell surface. In contrast, TGF-Β3, but not testosterone, induced the level of ubiquitin-conjugating enzyme E2 J1 (Ube2j1), a protein crucial to the intracellular protein degradation pathway, and its association with internalized occludin. Based on these findings and recent reports in the field, we hypothesize that the concerted effects of testosterone and TGF-Β3 likely facilitate the transit of preleptotene spermatocytes at the BTB while maintaining the immunological barrier in that testosterone induces the assembly of "new" tight junction (TJ)-fibrils below migrating spermatocytes via protein transcytosis and recycling before cytokines induce the disassembly of "old" TJ-fibrils above spermatocytes via endocytic vesicle-mediated degradation of internalized proteins. This thus provides a unique mechanism in the testis to facilitate the transit of preleptotene spermatocytes, many of which are connected in "clones" via cytoplasmic bridges, at the BTB while maintaining the immunological barrier during stage VIII of the seminiferous epithelial cycle of spermatogenesis. © 2010 Elsevier Inc.
Persistent Identifierhttp://hdl.handle.net/10722/140893
ISSN
2015 Impact Factor: 3.378
2015 SCImago Journal Rankings: 1.900
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of Health, (NICHD)R01 HD056034
R03 HD061401
University of Hong Kong
Hong Kong Research Grants Council
Funding Information:

This work was supported in part by grants from National Institutes of Health, (NICHD, R01 HD056034 to CYC; R03 HD061401 to DDM). W.M.L. was supported by a grant from University of Hong Kong CRCG Small Project Funding and Hong Kong Research Grants Council. L.S. was supported by a Postgraduate Student Research Award fellowship from the University of Hong Kong.

References

 

DC FieldValueLanguage
dc.contributor.authorSu, Len_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2011-09-23T06:21:01Z-
dc.date.available2011-09-23T06:21:01Z-
dc.date.issued2010en_HK
dc.identifier.citationExperimental Cell Research, 2010, v. 316 n. 17, p. 2945-2960en_HK
dc.identifier.issn0014-4827en_HK
dc.identifier.urihttp://hdl.handle.net/10722/140893-
dc.description.abstractThe intricate interaction between protein endocytosis, transcytosis, recycling and endosome- or ubiquitin-mediated protein degradation determines the junction integrity in epithelial cells including Sertoli cells at the blood-testis barrier (BTB). Studies have shown that androgens and cytokines (e.g., TGF-Β3) that are known to promote and disrupt BTB integrity, respectively, accelerate protein endocytosis at the BTB. We hypothesized that testosterone-induced endocytosed proteins are transcytosed and recycled back to the Sertoli cell surface, whereas cytokine-induced endocytosed proteins are degraded so that androgens and cytokines have opposing effects on BTB integrity. Herein, we report that both testosterone and TGF-Β3 induced the steady-state level of clathrin, an endocytic vesicle protein. Testosterone and TGF-Β3 also induced the association between internalized occludin (a BTB integral membrane protein) and clathrin, as well as early endosome antigen-1 (EEA-1). Interestingly, testosterone, but not TGF-Β3, also induced the levels of proteins that regulate protein transcytosis (e.g., caveolin-1) and recycling (e.g., Rab11), and their association with internalized occludin and N-cadherin from the cell surface. In contrast, TGF-Β3, but not testosterone, induced the level of ubiquitin-conjugating enzyme E2 J1 (Ube2j1), a protein crucial to the intracellular protein degradation pathway, and its association with internalized occludin. Based on these findings and recent reports in the field, we hypothesize that the concerted effects of testosterone and TGF-Β3 likely facilitate the transit of preleptotene spermatocytes at the BTB while maintaining the immunological barrier in that testosterone induces the assembly of "new" tight junction (TJ)-fibrils below migrating spermatocytes via protein transcytosis and recycling before cytokines induce the disassembly of "old" TJ-fibrils above spermatocytes via endocytic vesicle-mediated degradation of internalized proteins. This thus provides a unique mechanism in the testis to facilitate the transit of preleptotene spermatocytes, many of which are connected in "clones" via cytoplasmic bridges, at the BTB while maintaining the immunological barrier during stage VIII of the seminiferous epithelial cycle of spermatogenesis. © 2010 Elsevier Inc.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/yexcren_HK
dc.relation.ispartofExperimental Cell Researchen_HK
dc.subjectBlood-testis barrieren_HK
dc.subjectEndosome-mediated protein degradationen_HK
dc.subjectProtein endocytosisen_HK
dc.subjectProtein recyclingen_HK
dc.subjectProtein transcytosisen_HK
dc.subjectSeminiferous epithelial cycleen_HK
dc.subjectSpermatogenesisen_HK
dc.subjectTestisen_HK
dc.subjectTestosteroneen_HK
dc.subjectTGF-Β3en_HK
dc.subject.meshBlood-Testis Barrier - metabolism-
dc.subject.meshSpermatocytes - physiology-
dc.subject.meshTestosterone - pharmacology-
dc.subject.meshTransforming Growth Factor beta3 - pharmacology-
dc.subject.meshTransport Vesicles - metabolism-
dc.titleDifferential effects of testosterone and TGF-Β3 on endocytic vesicle-mediated protein trafficking events at the blood-testis barrieren_HK
dc.typeArticleen_HK
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.yexcr.2010.07.018en_HK
dc.identifier.pmid20682309-
dc.identifier.pmcidPMC2945409-
dc.identifier.scopuseid_2-s2.0-77956885122en_HK
dc.identifier.hkuros194364en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956885122&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume316en_HK
dc.identifier.issue17en_HK
dc.identifier.spage2945en_HK
dc.identifier.epage2960en_HK
dc.identifier.isiWOS:000282357300022-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridSu, L=34871019700en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK
dc.identifier.citeulike7603470-

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