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Article: Restricted Arp3 expression in the testis prevents blood-testis barrier disruption during junction restructuring at spermatogenesis

TitleRestricted Arp3 expression in the testis prevents blood-testis barrier disruption during junction restructuring at spermatogenesis
Authors
KeywordsActin dynamics
Ectoplasmic specialization
Seminiferous epithelial cycle
Spermiogenesis
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. 11411-11416 How to Cite?
AbstractIn epithelia, a primary damage of tight junctions (TJ) always leads to a secondary disruption of adherens junction (AJ), and vice versa. This response, if occurring in the testis, would disrupt spermatogenesis because the blood-testis barrier (BTB) must remain intact during the transit of spermatids in the seminiferous epithelium, which is associated with extensive apical ectoplasmic specialization (apical ES, a testis-specific AJ type) restructuring. As such, apical ES restructuring accompanied with the transit of developing spermatids during spermiogenesis must be segregated from the BTB to avoid an immunological barrier breakdown in all stages of the seminiferous epithelial cycle, except at stage VIII when spermiation and BTB restructuring take place concurrently. We report herein a mechanism involving restricted spatial and temporal expression of Arp2/3 complex and N-WASP, whose actin branching activity associated with apical ES and BTB restructuring in the seminiferous epithelium. High expression of Arp3 at the apical ES was shown to correlate with spermatid movement and proper spermatid orientation. Likewise, high Arp3 level at the BTB associated with its restructuring to accommodate the transit of preleptotene spermatocytes at stage VIII of the epithelial cycle. These findings were validated by in vitro and in vivo studies using wiskostatin, an inhibitor that blocks N-WASP from activating Arp2/3 complex to elicit actin branching. Inhibition of actin branching caused a failure of spermatid transit plus a loss of proper orientation in the epithelium, and a "tightened" Sertoli cell TJ permeability barrier, supporting the role of Arp2/3 complex in segregating the events of AJ and BTB restructuring.
Persistent Identifierhttp://hdl.handle.net/10722/127454
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
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.) and U54 HD029990 Project 5 (to C.Y.C.); and Hong Kong Research Grants Council Grant HKU7693/07M and the University of Hong Kong CRCG Seeding Funding (to W.M.L.).

References

 

DC FieldValueLanguage
dc.contributor.authorLie, PPYen_HK
dc.contributor.authorChan, AYNen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLee, WMen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2010-10-31T13:26:29Z-
dc.date.available2010-10-31T13:26:29Z-
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. 11411-11416en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/127454-
dc.description.abstractIn epithelia, a primary damage of tight junctions (TJ) always leads to a secondary disruption of adherens junction (AJ), and vice versa. This response, if occurring in the testis, would disrupt spermatogenesis because the blood-testis barrier (BTB) must remain intact during the transit of spermatids in the seminiferous epithelium, which is associated with extensive apical ectoplasmic specialization (apical ES, a testis-specific AJ type) restructuring. As such, apical ES restructuring accompanied with the transit of developing spermatids during spermiogenesis must be segregated from the BTB to avoid an immunological barrier breakdown in all stages of the seminiferous epithelial cycle, except at stage VIII when spermiation and BTB restructuring take place concurrently. We report herein a mechanism involving restricted spatial and temporal expression of Arp2/3 complex and N-WASP, whose actin branching activity associated with apical ES and BTB restructuring in the seminiferous epithelium. High expression of Arp3 at the apical ES was shown to correlate with spermatid movement and proper spermatid orientation. Likewise, high Arp3 level at the BTB associated with its restructuring to accommodate the transit of preleptotene spermatocytes at stage VIII of the epithelial cycle. These findings were validated by in vitro and in vivo studies using wiskostatin, an inhibitor that blocks N-WASP from activating Arp2/3 complex to elicit actin branching. Inhibition of actin branching caused a failure of spermatid transit plus a loss of proper orientation in the epithelium, and a "tightened" Sertoli cell TJ permeability barrier, supporting the role of Arp2/3 complex in segregating the events of AJ and BTB restructuring.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.subjectActin dynamicsen_HK
dc.subjectEctoplasmic specializationen_HK
dc.subjectSeminiferous epithelial cycleen_HK
dc.subjectSpermiogenesisen_HK
dc.subject.meshActin-Related Protein 3 - metabolism-
dc.subject.meshAnimals-
dc.subject.meshBlood-Testis Barrier - metabolism-
dc.subject.meshSpermatogenesis-
dc.subject.meshTight Junctions - metabolism-
dc.titleRestricted Arp3 expression in the testis prevents blood-testis barrier disruption during junction restructuring at spermatogenesisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8424&volume=107&issue=25&spage=11411&epage=11416&date=2010&atitle=Restricted+Arp3+expression+in+the+testis+prevents+blood-testis+barrier+disruption+during+junction+restructuring+at+spermatogenesis-
dc.identifier.emailLee, WM: hrszlwm@hku.hken_HK
dc.identifier.authorityLee, WM=rp00728en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1001823107en_HK
dc.identifier.pmid20534520-
dc.identifier.pmcidPMC2895132-
dc.identifier.scopuseid_2-s2.0-77954920588en_HK
dc.identifier.hkuros179026en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954920588&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume107en_HK
dc.identifier.issue25en_HK
dc.identifier.spage11411en_HK
dc.identifier.epage11416en_HK
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000279058000048-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLie, PPY=15839862700en_HK
dc.identifier.scopusauthoridChan, AYN=36185017800en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLee, WM=24799156600en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK

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