Rab8 Binding to Immune Cell-Specific Adaptor LAX Facilitates Formation of <i>trans</i>-Golgi Network-Proximal CTLA-4 Vesicles for Surface Expression
dc.contributor.author | Banton, Matthew | |
dc.contributor.author | Inder, KL | |
dc.contributor.author | Valk, E | |
dc.contributor.author | Rudd, CE | |
dc.contributor.author | Schneider, H | |
dc.date.accessioned | 2020-04-06T10:11:22Z | |
dc.date.available | 2020-04-06T10:11:22Z | |
dc.date.issued | 2014-04-01 | |
dc.identifier.issn | 0270-7306 | |
dc.identifier.issn | 1098-5549 | |
dc.identifier.uri | http://hdl.handle.net/10026.1/15498 | |
dc.description.abstract |
Despite playing a central role in tolerance, little is known regarding the mechanism by which intracellular CTLA-4 is shuttled from the trans-Golgi network to the surfaces of T cells. In this context, Ras-related GTPase Rab8 plays an important role in the intracellular transport, while we have previously shown that CTLA-4 binds to the immune cell adaptor TRIM in T cells. In this study, we demonstrate that CTLA-4 forms a multimeric complex comprised of TRIM and related LAX that in turn binds to GTP bound Rab8 for post-Golgi transport to the cell surface. LAX bound via its N terminus to active GTP-Rab8, as well as the cytoplasmic tail of CTLA-4. TRIM required LAX for binding to Rab8 in a complex. Wild-type LAX or its N terminus (residues 1 to 77) increased CTLA-4 surface expression, whereas small interfering RNAs of Rab8 or LAX or disruption of LAX/Rab8 binding reduced numbers of CTLA-4-containing vesicles and its coreceptor surface expression. LAX also promoted the polarization of CTLA-4 and the reorientation of the microtubule-organizing center to the site of T-cell receptor engagement. Our results identify a novel CTLA-4/TRIM/LAX/Rab8 effector complex in the transport of CTLA-4 to the surfaces of T cells. | |
dc.format.extent | 1486-1499 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | eng | |
dc.publisher | Informa UK Limited | |
dc.subject | Adaptor Proteins, Vesicular Transport | |
dc.subject | Animals | |
dc.subject | CTLA-4 Antigen | |
dc.subject | Cell Culture Techniques | |
dc.subject | Cell Line | |
dc.subject | Cell Membrane | |
dc.subject | Germinal Center Kinases | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Monomeric GTP-Binding Proteins | |
dc.subject | Protein Serine-Threonine Kinases | |
dc.subject | Protein Transport | |
dc.subject | Receptors, Antigen, T-Cell | |
dc.subject | T-Lymphocytes | |
dc.subject | trans-Golgi Network | |
dc.title | Rab8 Binding to Immune Cell-Specific Adaptor LAX Facilitates Formation of <i>trans</i>-Golgi Network-Proximal CTLA-4 Vesicles for Surface Expression | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000333338600010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 8 | |
plymouth.volume | 34 | |
plymouth.publication-status | Published | |
plymouth.journal | Molecular and Cellular Biology | |
dc.identifier.doi | 10.1128/mcb.01331-13 | |
plymouth.organisational-group | /Plymouth | |
plymouth.organisational-group | /Plymouth/Faculty of Health | |
plymouth.organisational-group | /Plymouth/Faculty of Health/School of Biomedical Sciences | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA | |
plymouth.organisational-group | /Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine | |
plymouth.organisational-group | /Plymouth/Users by role | |
plymouth.organisational-group | /Plymouth/Users by role/Academics | |
dc.publisher.place | United States | |
dc.identifier.eissn | 1098-5549 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1128/mcb.01331-13 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.type | Journal Article/Review |