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Article: Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells

TitleBlood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells
Authors
KeywordsBasal ectoplasmic specialization
Preleptotene spermatocyte migration
Seminiferous epithelial cycle
Spermatogenesis
Tight junction
Issue Date2008
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
FASEB Journal, 2008, v. 22 n. 6, p. 1945-1959 How to Cite?
AbstractDuring spermatogenesis in the mammalian testis, preleptotene/leptotene spermatocytes differentiate from type B spermatogonia and traverse the blood-testis barrier (BTB) at stage VIII of the seminiferous epithelial cycle for further development. This timely movement of germ cells involves extensive junction restructuring at the BTB. Previous studies have shown that these events are regulated by testosterone (T) and cytokines [e.g., the transforming growth factor (TGF) -βs], which promote and disrupt the BTB assembly, respectively. However, the mechanisms underlying the "opening" of the BTB above a migrating preleptotene/leptotene spermatocyte and the "resealing" of the barrier underneath this cell remain obscure. We now report findings on a novel mechanism utilized by the testes to regulate these events. Using cell surface protein biotinylation coupled with immunoblotting and immunofluorescent microscopy, we assessed the kinetics of endocytosis and recycling of BTB-associated integral membrane proteins: occludin, JAM-A, and N-cadherin. It was shown that these proteins were continuously endocytosed and recycled back to the Sertoli cell surface via the clathrin-mediated but not the caveolin-mediated pathway. When T or TGF-β2 was added to Sertoli cell cultures with established functional BTB, both factors accelerated the kinetics of internalization of BTB proteins from the cell surface, perhaps above the migrating preleptotene spermatocyte, thereby opening the BTB. Likewise, T also enhanced the kinetics of recycling of internalized biotinylated proteins back to the cell surface, plausibly relocating these proteins beneath the migrating spermatocyte to reassemble the BTB. In contrast, TGF-β2 targeted internalized biotinylated proteins to late endosomes for degradation, destabilizing the BTB. In summary, the transient opening of the BTB that facilitates germ cell movement is mediated via the differential effects of T and cytokines on the kinetics of endocytosis and recycling of integral membrane proteins at the BTB. The net result of these interactions, in turn, determines the steady-state protein levels at the Sertoli-Sertoli cell interface at the BTB. © FASEB.
Persistent Identifierhttp://hdl.handle.net/10722/89286
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYan, HHNen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2010-09-06T09:54:56Z-
dc.date.available2010-09-06T09:54:56Z-
dc.date.issued2008en_HK
dc.identifier.citationFASEB Journal, 2008, v. 22 n. 6, p. 1945-1959en_HK
dc.identifier.issn0892-6638en_HK
dc.identifier.urihttp://hdl.handle.net/10722/89286-
dc.description.abstractDuring spermatogenesis in the mammalian testis, preleptotene/leptotene spermatocytes differentiate from type B spermatogonia and traverse the blood-testis barrier (BTB) at stage VIII of the seminiferous epithelial cycle for further development. This timely movement of germ cells involves extensive junction restructuring at the BTB. Previous studies have shown that these events are regulated by testosterone (T) and cytokines [e.g., the transforming growth factor (TGF) -βs], which promote and disrupt the BTB assembly, respectively. However, the mechanisms underlying the "opening" of the BTB above a migrating preleptotene/leptotene spermatocyte and the "resealing" of the barrier underneath this cell remain obscure. We now report findings on a novel mechanism utilized by the testes to regulate these events. Using cell surface protein biotinylation coupled with immunoblotting and immunofluorescent microscopy, we assessed the kinetics of endocytosis and recycling of BTB-associated integral membrane proteins: occludin, JAM-A, and N-cadherin. It was shown that these proteins were continuously endocytosed and recycled back to the Sertoli cell surface via the clathrin-mediated but not the caveolin-mediated pathway. When T or TGF-β2 was added to Sertoli cell cultures with established functional BTB, both factors accelerated the kinetics of internalization of BTB proteins from the cell surface, perhaps above the migrating preleptotene spermatocyte, thereby opening the BTB. Likewise, T also enhanced the kinetics of recycling of internalized biotinylated proteins back to the cell surface, plausibly relocating these proteins beneath the migrating spermatocyte to reassemble the BTB. In contrast, TGF-β2 targeted internalized biotinylated proteins to late endosomes for degradation, destabilizing the BTB. In summary, the transient opening of the BTB that facilitates germ cell movement is mediated via the differential effects of T and cytokines on the kinetics of endocytosis and recycling of integral membrane proteins at the BTB. The net result of these interactions, in turn, determines the steady-state protein levels at the Sertoli-Sertoli cell interface at the BTB. © FASEB.en_HK
dc.languageengen_HK
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/en_HK
dc.relation.ispartofFASEB Journalen_HK
dc.subjectBasal ectoplasmic specializationen_HK
dc.subjectPreleptotene spermatocyte migrationen_HK
dc.subjectSeminiferous epithelial cycleen_HK
dc.subjectSpermatogenesisen_HK
dc.subjectTight junctionen_HK
dc.titleBlood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0892-6638&volume=22&spage=1945&epage=69&date=2008&atitle=Blood-testis+barrier+dynamics+are+regulated+by+testosterone+and+cytokines+via+their+differential+effects+on+the+kinetics+of+protein+endocytosis+and+recycling+in+Sertoli+cells.+en_HK
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1096/fj.06-070342en_HK
dc.identifier.pmid18192323-
dc.identifier.pmcidPMC2804916-
dc.identifier.scopuseid_2-s2.0-44949190438en_HK
dc.identifier.hkuros149047en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-44949190438&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume22en_HK
dc.identifier.issue6en_HK
dc.identifier.spage1945en_HK
dc.identifier.epage1959en_HK
dc.identifier.isiWOS:000256352700034-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYan, HHN=14018807300en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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