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Article: Regulation of blood-testis barrier dynamics by TGF-β3 is a Cdc42-dependent protein trafficking event

TitleRegulation of blood-testis barrier dynamics by TGF-β3 is a Cdc42-dependent protein trafficking event
Authors
KeywordsCytokines
GTPases
Protein endocytosis
Seminiferous epithelial cycle
Spermatogenesis
Issue Date2010
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 25, p. 11399-11404 How to Cite?
AbstractIn the testis, the blood-testis barrier (BTB) is constituted by specialized junctions between adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. Although the BTB is one of the tightest blood-tissue barriers in the mammalian body, it undergoes extensive restructuring at stage VIII of the seminiferous epithelial cycle to facilitate the transit of preleptotene spermatocytes. Thus, meiosis and postmeiotic germ cell development take place in the seminiferous epithelium behind the BTB. Cytokines (e.g., TGF-β3) are known to regulate BTB dynamics by enhancing the endocytosis of integral membrane proteins and their intracellular degradation. This thus reduces the levels of proteins above the spermatocytes in transit at the BTB, causing its disruption after testosterone-induced new tight junction (TJ) fibrils are formed behind these cells. By using Sertoli cells cultured in vitro with an established TJ permeability barrier that mimicked the BTB in vivo, Cdc42 was shown to be a crucial regulator that mediated the TGF-β3-induced BTB disruption. TGF-β3 was shown to activate Cdc42 to its active GTP-bound form. However, an inactivation of Cdc42 by overexpressing its dominant-negative mutant T17N in Sertoli cell epithelium was shown to block the TGF-β3-induced acceleration in protein endocytosis. Consequently, this prevented the disruption of Sertoli cell TJ permeability barrier and redistribution of TJ proteins (e.g., CAR and ZO-1) from the cell-cell interface to cell cytosol caused by TGF-β3. In summary, Cdc42 is a crucial regulatory component in the TGF-β3-mediated cascade of events that leads to the disruption of the TJ fibrils above the preleptotene spermatocytes to facilitate their transit.
Persistent Identifierhttp://hdl.handle.net/10722/127452
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
National Institutes of Health/National Institute of Child Health and Human DevelopmentR01 HD056034
U54 HD029990
R03 HD061401
Hong Kong Research Grants CouncilHKU7693/07M
Funding Information:

This work was supported by National Institutes of Health/National Institute of Child Health and Human Development Grants R01 HD056034 (to C.Y.C.) U54 HD029990 Project 5 (to C.Y.C.) and R03 HD061401 (to D.D.M.); Hong Kong Research Grants Council Grant HKU7693/07M(to W.M.L.).

References

 

DC FieldValueLanguage
dc.contributor.authorWong, EWPen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2010-10-31T13:26:23Z-
dc.date.available2010-10-31T13:26:23Z-
dc.date.issued2010en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2010, v. 107 n. 25, p. 11399-11404en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127452-
dc.description.abstractIn the testis, the blood-testis barrier (BTB) is constituted by specialized junctions between adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. Although the BTB is one of the tightest blood-tissue barriers in the mammalian body, it undergoes extensive restructuring at stage VIII of the seminiferous epithelial cycle to facilitate the transit of preleptotene spermatocytes. Thus, meiosis and postmeiotic germ cell development take place in the seminiferous epithelium behind the BTB. Cytokines (e.g., TGF-β3) are known to regulate BTB dynamics by enhancing the endocytosis of integral membrane proteins and their intracellular degradation. This thus reduces the levels of proteins above the spermatocytes in transit at the BTB, causing its disruption after testosterone-induced new tight junction (TJ) fibrils are formed behind these cells. By using Sertoli cells cultured in vitro with an established TJ permeability barrier that mimicked the BTB in vivo, Cdc42 was shown to be a crucial regulator that mediated the TGF-β3-induced BTB disruption. TGF-β3 was shown to activate Cdc42 to its active GTP-bound form. However, an inactivation of Cdc42 by overexpressing its dominant-negative mutant T17N in Sertoli cell epithelium was shown to block the TGF-β3-induced acceleration in protein endocytosis. Consequently, this prevented the disruption of Sertoli cell TJ permeability barrier and redistribution of TJ proteins (e.g., CAR and ZO-1) from the cell-cell interface to cell cytosol caused by TGF-β3. In summary, Cdc42 is a crucial regulatory component in the TGF-β3-mediated cascade of events that leads to the disruption of the TJ fibrils above the preleptotene spermatocytes to facilitate their transit.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.rightsNational Academy of Sciences. Proceedings. Copyright © National Academy of Sciences.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCytokinesen_HK
dc.subjectGTPasesen_HK
dc.subjectProtein endocytosisen_HK
dc.subjectSeminiferous epithelial cycleen_HK
dc.subjectSpermatogenesisen_HK
dc.subject.meshBlood - metabolism-
dc.subject.meshBlood-Testis Barrier - metabolism-
dc.subject.meshTestis - metabolism-
dc.subject.meshTransforming Growth Factor beta3 - metabolism-
dc.subject.meshCdc42 GTP-Binding Protein - metabolism-
dc.titleRegulation of blood-testis barrier dynamics by TGF-β3 is a Cdc42-dependent protein trafficking eventen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=107&issue=25&spage=11399&epage=11404&date=2010&atitle=Regulation+of+blood-testis+barrier+dynamics+by+TGF-ß3+is+a+Cdc42-dependent+protein+trafficking+event-
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1073/pnas.1001077107en_HK
dc.identifier.pmid20534521-
dc.identifier.pmcidPMC2895131-
dc.identifier.scopuseid_2-s2.0-77954917321en_HK
dc.identifier.hkuros179024en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954917321&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume107en_HK
dc.identifier.issue25en_HK
dc.identifier.spage11399en_HK
dc.identifier.epage11404en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000279058000046-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridWong, EWP=23029194700en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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