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Article: Sertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LIMK signaling pathway

TitleSertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LIMK signaling pathway
Authors
KeywordsSertoli cells
Signal transduction
Sperm
Spermatogenesis
Testis
Issue Date2003
PublisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/
Citation
Biology Of Reproduction, 2003, v. 68 n. 6, p. 2189-2206 How to Cite?
AbstractDuring spermatogenesis, cell-cell actin-based adherens junctions (AJs), such as ectoplasmic specializations (ESs), between Sertoli and germ cells undergo extensive restructuring in the seminiferous epithelium to facilitate germ cell movement across the epithelium. Although the mechanism(s) that regulates AJ dynamics in the testis is virtually unknown, Rho GTPases have been implicated in the regulation of these events in other epithelia. Studies have shown that the in vitro assembly of the Sertoli-germ cell AJs but not of the Sertoli cell tight junctions (TJs) is associated with a transient but significant induction of RhoB. Immunohistochemistry has shown that the localization of RhoB in the seminiferous epithelium is stage specific, being lowest in stages VII-VIII prior to spermiation, and displays cell-specific association during the epithelial cycle. Throughout the cycle, RhoB was localized near the site of basal and apical ESs but was restricted to the periphery of the nuclei in elongating (but not elongated) spermatids, spermatocytes, and Sertoli cells. However, RhoB was not detected near the site of apical ESs at stages VII-VIII. Furthermore, disruption of AJs in Sertoli-germ cell cocultures either by hypotonic treatment or by treatment with 1(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364) also induced RhoB expression. When adult rats were treated with AF-2364 to perturb Sertoli-germ cell AJs in vivo, a ∼4-fold induction in RhoB in the testis, but not in kidney and brain, was detected within 1 h, at least -1-4 days before germ cell loss from the epithelium could be detected by histological analysis. The signaling pathway(s) by which AF-2364 perturbed the Sertoligerm cell AJs apparently began with an initial activation of integrin, which in turn activated RhoB, ROCK1, (Rho-associated protein kinase 1, also called ROKβ), LIMK1 (LIM-kinase-1, also called lin-11 isl-1 mec3 kinase 1), and cofilin but not p140mDia and profilin via phosphorylation. Immunoprecipitation and immunoblots revealed that the induction of LIMK1 was mediated via an increase in its phospho-Ser but not phospho-Tyr content. Furthermore, Y-27632 ([(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane-carboxamide, 2HCl]), a specific ROCK inhibitor, could effectively delay the AF-2364-induced germ cell loss from the seminiferous epithelium in vivo, illustrating that the integrin/RhoB/ROCK/LIMK pathway indeed plays a crucial role in the regulation of Sertoli-germ cell AJ dynamics. The fact that the RhoB pathway in the kidney and brain was not activated suggests that AF-2364 exerts its effects primarily at the testisspecific ES multiprotein complex structures between Sertoli cells and spermatids. In summary, this report illustrates that Sertoli germ cell AJ dynamics are regulated, at least in part, via the integrin/ROCK/LIMK/cofilin signaling pathway.
Persistent Identifierhttp://hdl.handle.net/10722/84739
ISSN
2015 Impact Factor: 3.471
2015 SCImago Journal Rankings: 1.646
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLui, WYen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2010-09-06T08:56:33Z-
dc.date.available2010-09-06T08:56:33Z-
dc.date.issued2003en_HK
dc.identifier.citationBiology Of Reproduction, 2003, v. 68 n. 6, p. 2189-2206en_HK
dc.identifier.issn0006-3363en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84739-
dc.description.abstractDuring spermatogenesis, cell-cell actin-based adherens junctions (AJs), such as ectoplasmic specializations (ESs), between Sertoli and germ cells undergo extensive restructuring in the seminiferous epithelium to facilitate germ cell movement across the epithelium. Although the mechanism(s) that regulates AJ dynamics in the testis is virtually unknown, Rho GTPases have been implicated in the regulation of these events in other epithelia. Studies have shown that the in vitro assembly of the Sertoli-germ cell AJs but not of the Sertoli cell tight junctions (TJs) is associated with a transient but significant induction of RhoB. Immunohistochemistry has shown that the localization of RhoB in the seminiferous epithelium is stage specific, being lowest in stages VII-VIII prior to spermiation, and displays cell-specific association during the epithelial cycle. Throughout the cycle, RhoB was localized near the site of basal and apical ESs but was restricted to the periphery of the nuclei in elongating (but not elongated) spermatids, spermatocytes, and Sertoli cells. However, RhoB was not detected near the site of apical ESs at stages VII-VIII. Furthermore, disruption of AJs in Sertoli-germ cell cocultures either by hypotonic treatment or by treatment with 1(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364) also induced RhoB expression. When adult rats were treated with AF-2364 to perturb Sertoli-germ cell AJs in vivo, a ∼4-fold induction in RhoB in the testis, but not in kidney and brain, was detected within 1 h, at least -1-4 days before germ cell loss from the epithelium could be detected by histological analysis. The signaling pathway(s) by which AF-2364 perturbed the Sertoligerm cell AJs apparently began with an initial activation of integrin, which in turn activated RhoB, ROCK1, (Rho-associated protein kinase 1, also called ROKβ), LIMK1 (LIM-kinase-1, also called lin-11 isl-1 mec3 kinase 1), and cofilin but not p140mDia and profilin via phosphorylation. Immunoprecipitation and immunoblots revealed that the induction of LIMK1 was mediated via an increase in its phospho-Ser but not phospho-Tyr content. Furthermore, Y-27632 ([(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexane-carboxamide, 2HCl]), a specific ROCK inhibitor, could effectively delay the AF-2364-induced germ cell loss from the seminiferous epithelium in vivo, illustrating that the integrin/RhoB/ROCK/LIMK pathway indeed plays a crucial role in the regulation of Sertoli-germ cell AJ dynamics. The fact that the RhoB pathway in the kidney and brain was not activated suggests that AF-2364 exerts its effects primarily at the testisspecific ES multiprotein complex structures between Sertoli cells and spermatids. In summary, this report illustrates that Sertoli germ cell AJ dynamics are regulated, at least in part, via the integrin/ROCK/LIMK/cofilin signaling pathway.en_HK
dc.languageengen_HK
dc.publisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/en_HK
dc.relation.ispartofBiology of Reproductionen_HK
dc.subjectSertoli cellsen_HK
dc.subjectSignal transductionen_HK
dc.subjectSpermen_HK
dc.subjectSpermatogenesisen_HK
dc.subjectTestisen_HK
dc.titleSertoli-germ cell adherens junction dynamics in the testis are regulated by RhoB GTPase via the ROCK/LIMK signaling pathwayen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0006-3363&volume=68&spage=2189&epage=2206&date=2003&atitle=Sertoli-Germ+Cell+Adherens+Junction+Dynamics+in+the+Testis+Are+Regulated+by+RhoB+GTPase+via+the+ROCK/LIMK+Signaling+Pathwayen_HK
dc.identifier.emailLui, WY: wylui@hku.hken_HK
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLui, WY=rp00756en_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1095/biolreprod.102.011379en_HK
dc.identifier.pmid12606349-
dc.identifier.scopuseid_2-s2.0-0038513420en_HK
dc.identifier.hkuros81244en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0038513420&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume68en_HK
dc.identifier.issue6en_HK
dc.identifier.spage2189en_HK
dc.identifier.epage2206en_HK
dc.identifier.isiWOS:000183130000031-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLui, WY=35220192400en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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