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Article: Sertoli cell–specific coxsackievirus and adenovirus receptor regulates cell adhesion and gene transcription via β-catenin inactivation and Cdc42 activation

TitleSertoli cell–specific coxsackievirus and adenovirus receptor regulates cell adhesion and gene transcription via β-catenin inactivation and Cdc42 activation
Authors
Keywordsblood–testis
barrierectoplasmic specialization
reproductive impairment
spermatogenesis
Issue Date2019
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
The FASEB Journal, 2019, v. 33 n. 6, p. 7588-7602 How to Cite?
AbstractBlood-testis barrier (BTB) and apical ectoplasmic specialization (ES) serve as structural supports for germ cell (GC) development. We demonstrated that the Sertoli cell (SC)-specific coxsackievirus and adenovirus receptor (CXADR) knockout (SC-CXADR−/−), but not the GC-specific knockout, impaired spermatogenesis. An increase in GC apoptosis and premature loss of elongated spermatids were observed in SC-CXADR−/− testes. The BTB function was compromised in SC-CXADR−/− testes with dysregulation of oocludin and zonula occludens-1 expression at the basal compartment of the seminiferous epithelium. An integrated omics analyses confirmed that altered gene ontology terms identified in SC-CXADR−/− testes are highly associated with spermatid development and differentiation, spermatogenesis, and sperm motility and are considered as unique testicular function terms. Leptin, Nasp, Tektin3, Larp 7, and acrosin, which are highly associated with male fertility, were found to be down-regulated in SC-CXADR−/− testes. Based on the data from the omics analyses, we employed the CXADR-deficient SC model to further investigate the molecular mechanisms involved. We unraveled that SC-CXADRs are required for β-catenin inactivation and cell division cycle protein 42 (Cdc42) activation, resulting in maintaining the integrity and function of the BTB and apical ES as well as inhibiting gene transcription, such as the Myc gene, in the testes. We demonstrated for the first time that CXADR is an important mediator governing β-catenin and Cdc42 signaling that is essential for spermatogenesis. The molecular mechanisms identified herein may provide new insights to unravel the novel functions and signaling cascades of CXADR in other key CXADR-expressing tissues.—Huang, K., Ru, B., Zhang, Y., Chan, W.-L., Chow, S.-C., Zhang, J., Lo, C., Lui, W.-Y. Sertoli cell–specific coxsackievirus and adenovirus receptor regulates cell adhesion and gene transcription via β-catenin inactivation and Cdc42 activation.
Persistent Identifierhttp://hdl.handle.net/10722/276029
ISSN
2017 Impact Factor: 5.595
2015 SCImago Journal Rankings: 2.775

 

DC FieldValueLanguage
dc.contributor.authorHuang, K-
dc.contributor.authorRu, B-
dc.contributor.authorZhang, Y-
dc.contributor.authorChan, WL-
dc.contributor.authorChow, SC-
dc.contributor.authorZhang, J-
dc.contributor.authorLo, CSC-
dc.contributor.authorLui, WY-
dc.date.accessioned2019-09-10T02:54:29Z-
dc.date.available2019-09-10T02:54:29Z-
dc.date.issued2019-
dc.identifier.citationThe FASEB Journal, 2019, v. 33 n. 6, p. 7588-7602-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/276029-
dc.description.abstractBlood-testis barrier (BTB) and apical ectoplasmic specialization (ES) serve as structural supports for germ cell (GC) development. We demonstrated that the Sertoli cell (SC)-specific coxsackievirus and adenovirus receptor (CXADR) knockout (SC-CXADR−/−), but not the GC-specific knockout, impaired spermatogenesis. An increase in GC apoptosis and premature loss of elongated spermatids were observed in SC-CXADR−/− testes. The BTB function was compromised in SC-CXADR−/− testes with dysregulation of oocludin and zonula occludens-1 expression at the basal compartment of the seminiferous epithelium. An integrated omics analyses confirmed that altered gene ontology terms identified in SC-CXADR−/− testes are highly associated with spermatid development and differentiation, spermatogenesis, and sperm motility and are considered as unique testicular function terms. Leptin, Nasp, Tektin3, Larp 7, and acrosin, which are highly associated with male fertility, were found to be down-regulated in SC-CXADR−/− testes. Based on the data from the omics analyses, we employed the CXADR-deficient SC model to further investigate the molecular mechanisms involved. We unraveled that SC-CXADRs are required for β-catenin inactivation and cell division cycle protein 42 (Cdc42) activation, resulting in maintaining the integrity and function of the BTB and apical ES as well as inhibiting gene transcription, such as the Myc gene, in the testes. We demonstrated for the first time that CXADR is an important mediator governing β-catenin and Cdc42 signaling that is essential for spermatogenesis. The molecular mechanisms identified herein may provide new insights to unravel the novel functions and signaling cascades of CXADR in other key CXADR-expressing tissues.—Huang, K., Ru, B., Zhang, Y., Chan, W.-L., Chow, S.-C., Zhang, J., Lo, C., Lui, W.-Y. Sertoli cell–specific coxsackievirus and adenovirus receptor regulates cell adhesion and gene transcription via β-catenin inactivation and Cdc42 activation.-
dc.languageeng-
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/-
dc.relation.ispartofThe FASEB Journal-
dc.subjectblood–testis-
dc.subjectbarrierectoplasmic specialization-
dc.subjectreproductive impairment-
dc.subjectspermatogenesis-
dc.titleSertoli cell–specific coxsackievirus and adenovirus receptor regulates cell adhesion and gene transcription via β-catenin inactivation and Cdc42 activation-
dc.typeArticle-
dc.identifier.emailChow, SC: chowsc@hku.hk-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.emailLo, CSC: clivelo@hku.hk-
dc.identifier.emailLui, WY: wylui@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.identifier.authorityLo, CSC=rp00751-
dc.identifier.authorityLui, WY=rp00756-
dc.identifier.doi10.1096/fj.201801584R-
dc.identifier.scopuseid_2-s2.0-85067266375-
dc.identifier.hkuros302397-
dc.identifier.volume33-
dc.identifier.issue6-
dc.identifier.spage7588-
dc.identifier.epage7602-
dc.publisher.placeUnited States-

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