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Article: Regulation of sertoli-germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-β-catenin protein complex which are possibly mediated by c-Src and myotubularin-related protein 2: An in vivo study using an androgen suppression model

TitleRegulation of sertoli-germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-β-catenin protein complex which are possibly mediated by c-Src and myotubularin-related protein 2: An in vivo study using an androgen suppression model
Authors
KeywordsGene Expression Regulation
Germ Cells - cytology - metabolism
Immunoblotting
Sertoli Cells - cytology
Microscopy, Fluorescence
Issue Date2005
PublisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.org
Citation
Endocrinology, 2005, v. 146 n. 3, p. 1268-1284 How to Cite?
AbstractUsing a well characterized model of cell-cell actin-based adherens junction (AJ) disruption by suppressing the intratesticular testosterone level in adult rats with testosterone-estradiol implants, we have confirmed earlier findings that Sertoli-germ cell AJ dynamics are regulated by the activation of kinases via putative signaling pathways but with some unexpected findings as follows. First, the loss of germ cells from the seminiferous epithelium during androgen suppression was associated with a surge in myotubularin-related protein 2 (MTMR2, a lipid phosphatase, in which adult MTMH2-/- mice were recently shown to be azoospermic because of the loss of cell adhesion function between germ and Sertoli cells); kinases: phosphatidylinositol 3-kinase, c-Src, and C-terminal Src kinase; adaptors: α-actinin, vinculin, afadin, and p130 Crk-associated protein; and AJ-integral membrane proteins at the ectoplasmic specialization (ES, a testis-specific cell-cell actin-based AJ type) site: N-cadherin, β-catenin, integrin β1, and nectin 3. Second, MTMR2, instead of structurally interacting with phosphatidylinositol 3-kinase, a protein and lipid kinase, was shown to associate only with c-Src, a nonreceptor protein tyrosine kinase, as demonstrated by both coimmunoprecipitation and fluorescent microscopy at the site of apical ES, but none of the kinases, adaptors, and AJ-infegral proteins that were examined. Collectively, these results suggest that the MTMR2/c-Src is an important phosphatase/kinase protein pair in AJ dynamics in the testis. Because c-Src is known to associate with the cadherin/catenin protein complex at the ES in the testis, we next sought to investigate any changes in the protein-protein interactions of this protein complex during androgen suppression-induced germ cell loss. Indeed, there was a loss of N-cadherin and β-catenin association, accompanied by a surge in Tyr phosphorylation of β-catenin, during germ cell loss from the epithelium. Third, and perhaps the most important of all, during natural recovery of the epithelium after removal of testosterene-estradiol implants when spermatids were reattaching to Sertoli cells, an increase in N-cadherin and β-catenin association was detected with a concomitant loss in the increased Tyr phosphorylation in β-catenin. In summary, these results illustrate that the cadherin/catenin is a crucial cell adhesion complex that regulates AJ dynamics in the testis, and its functionality is likely modulated by the MTMR2/c-Src protein complex.
Persistent Identifierhttp://hdl.handle.net/10722/48688
ISSN
2023 Impact Factor: 3.8
2023 SCImago Journal Rankings: 1.285
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, Jen_HK
dc.contributor.authorWong, CHen_HK
dc.contributor.authorXia, Wen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, NPYen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2008-05-22T04:21:24Z-
dc.date.available2008-05-22T04:21:24Z-
dc.date.issued2005en_HK
dc.identifier.citationEndocrinology, 2005, v. 146 n. 3, p. 1268-1284en_HK
dc.identifier.issn0013-7227en_HK
dc.identifier.urihttp://hdl.handle.net/10722/48688-
dc.description.abstractUsing a well characterized model of cell-cell actin-based adherens junction (AJ) disruption by suppressing the intratesticular testosterone level in adult rats with testosterone-estradiol implants, we have confirmed earlier findings that Sertoli-germ cell AJ dynamics are regulated by the activation of kinases via putative signaling pathways but with some unexpected findings as follows. First, the loss of germ cells from the seminiferous epithelium during androgen suppression was associated with a surge in myotubularin-related protein 2 (MTMR2, a lipid phosphatase, in which adult MTMH2-/- mice were recently shown to be azoospermic because of the loss of cell adhesion function between germ and Sertoli cells); kinases: phosphatidylinositol 3-kinase, c-Src, and C-terminal Src kinase; adaptors: α-actinin, vinculin, afadin, and p130 Crk-associated protein; and AJ-integral membrane proteins at the ectoplasmic specialization (ES, a testis-specific cell-cell actin-based AJ type) site: N-cadherin, β-catenin, integrin β1, and nectin 3. Second, MTMR2, instead of structurally interacting with phosphatidylinositol 3-kinase, a protein and lipid kinase, was shown to associate only with c-Src, a nonreceptor protein tyrosine kinase, as demonstrated by both coimmunoprecipitation and fluorescent microscopy at the site of apical ES, but none of the kinases, adaptors, and AJ-infegral proteins that were examined. Collectively, these results suggest that the MTMR2/c-Src is an important phosphatase/kinase protein pair in AJ dynamics in the testis. Because c-Src is known to associate with the cadherin/catenin protein complex at the ES in the testis, we next sought to investigate any changes in the protein-protein interactions of this protein complex during androgen suppression-induced germ cell loss. Indeed, there was a loss of N-cadherin and β-catenin association, accompanied by a surge in Tyr phosphorylation of β-catenin, during germ cell loss from the epithelium. Third, and perhaps the most important of all, during natural recovery of the epithelium after removal of testosterene-estradiol implants when spermatids were reattaching to Sertoli cells, an increase in N-cadherin and β-catenin association was detected with a concomitant loss in the increased Tyr phosphorylation in β-catenin. In summary, these results illustrate that the cadherin/catenin is a crucial cell adhesion complex that regulates AJ dynamics in the testis, and its functionality is likely modulated by the MTMR2/c-Src protein complex.en_HK
dc.format.extent2206128 bytes-
dc.format.extent2457 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypetext/plain-
dc.languageengen_HK
dc.publisherThe Endocrine Society. The Journal's web site is located at http://endo.endojournals.orgen_HK
dc.relation.ispartofEndocrinologyen_HK
dc.rightsEndocrinology. Copyright © The Endocrine Society.en_HK
dc.subjectGene Expression Regulationen_HK
dc.subjectGerm Cells - cytology - metabolismen_HK
dc.subjectImmunoblottingen_HK
dc.subjectSertoli Cells - cytologyen_HK
dc.subjectMicroscopy, Fluorescenceen_HK
dc.titleRegulation of sertoli-germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-β-catenin protein complex which are possibly mediated by c-Src and myotubularin-related protein 2: An in vivo study using an androgen suppression modelen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0013-7227&volume=146&issue=3&spage=1268&epage=1284&date=2005&atitle=Regulation+of+Sertoli-germ+cell+adherens+junction+dynamics+via+changes+in+protein-protein+interactions+of+the+N-cadherin-beta-catenin+protein+complex+which+are+possibly+mediated+by+c-Src+and+myotubularin-related+protein+2:+an+in+vivo+study+using+an+androgen_HK
dc.identifier.emailLee, NPY: nikkilee@hku.hken_HK
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, NPY=rp00263en_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturepostprinten_HK
dc.identifier.doi10.1210/en.2004-1194en_HK
dc.identifier.pmid15591133-
dc.identifier.scopuseid_2-s2.0-14244270095en_HK
dc.identifier.hkuros98813-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-14244270095&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume146en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1268en_HK
dc.identifier.epage1284en_HK
dc.identifier.isiWOS:000227035400035-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhang, J=37065651400en_HK
dc.identifier.scopusauthoridWong, CH=8849630400en_HK
dc.identifier.scopusauthoridXia, W=8672244100en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, NPY=7402722690en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK
dc.identifier.issnl0013-7227-

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