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dc.contributor.authorJanssen, Erin
dc.contributor.authorTohme, Mira
dc.contributor.authorHedayat, Mona
dc.contributor.authorLeick, Marion
dc.contributor.authorRamesh, Narayanaswamy
dc.contributor.authorMassaad, Michel J.
dc.contributor.authorUllas, Sumana
dc.contributor.authorAzcutia, Veronica
dc.contributor.authorGoodnow, Christopher C.
dc.contributor.authorRandall, Katrina L.
dc.contributor.authorQiao, Qi
dc.contributor.authorWu, Hao
dc.contributor.authorAl-Herz, Waleed
dc.contributor.authorCox, Dianne
dc.contributor.authorHartwig, John
dc.contributor.authorLuscinskas, Francis W.
dc.contributor.authorGeha, Raif S.
dc.contributor.authorKumari, Sudha
dc.contributor.authorIrvine, Darrell J
dc.date.accessioned2017-04-07T18:06:48Z
dc.date.available2017-04-07T18:06:48Z
dc.date.issued2016-09
dc.date.submitted2015-12
dc.identifier.issn0021-9738
dc.identifier.issn1558-8238
dc.identifier.urihttp://hdl.handle.net/1721.1/107953
dc.description.abstractWiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor–driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that links TCRs to the actin cytoskeleton in TCR-driven actin assembly. Further, they provide an explanation for similarities in the clinical phenotypes of WAS and DOCK8 deficiency.en_US
dc.description.sponsorshipUnited States. Public Health Service (RO1AI114588)en_US
dc.description.sponsorshipUnited States. Public Health Service (K08AI114968 )en_US
dc.language.isoen_US
dc.publisherAmerican Society for Clinical Investigationen_US
dc.relation.isversionofhttp://dx.doi.org/10.1172/jci85774en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceAmerican Society for Clinical Investigationen_US
dc.titleA DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeletonen_US
dc.typeArticleen_US
dc.identifier.citationJanssen, Erin, Mira Tohme, Mona Hedayat, Marion Leick, Sudha Kumari, Narayanaswamy Ramesh, Michel J. Massaad, et al. “A DOCK8-WIP-WASp Complex Links T Cell Receptors to the Actin Cytoskeleton.” Journal of Clinical Investigation 126, no. 10 (September 6, 2016): 3837–3851. © 2016 American Society for Clinical Investigationen_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.mitauthorKumari, Sudha
dc.contributor.mitauthorIrvine, Darrell J
dc.relation.journalJournal of Clinical Investigationen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsJanssen, Erin; Tohme, Mira; Hedayat, Mona; Leick, Marion; Kumari, Sudha; Ramesh, Narayanaswamy; Massaad, Michel J.; Ullas, Sumana; Azcutia, Veronica; Goodnow, Christopher C.; Randall, Katrina L.; Qiao, Qi; Wu, Hao; Al-Herz, Waleed; Cox, Dianne; Hartwig, John; Irvine, Darrell J.; Luscinskas, Francis W.; Geha, Raif S.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2705-7245
mit.licensePUBLISHER_POLICYen_US


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