Rab8 binding to immune cell-specific adaptor LAX facilitates formation of trans-golgi network-proximal CTLA-4 vesicles for surface expression

Banton, Matthew C., Inder, Kerry L., Valk, Elke, Rudd, Christopher E. and Schneider, Helga (2014) Rab8 binding to immune cell-specific adaptor LAX facilitates formation of trans-golgi network-proximal CTLA-4 vesicles for surface expression. Molecular and Cellular Biology, 34 8: 1486-1499. doi:10.1128/MCB.01331-13


Author Banton, Matthew C.
Inder, Kerry L.
Valk, Elke
Rudd, Christopher E.
Schneider, Helga
Title Rab8 binding to immune cell-specific adaptor LAX facilitates formation of trans-golgi network-proximal CTLA-4 vesicles for surface expression
Formatted title
Rab8 binding to immune cell-specific adaptor LAX facilitates formation of trans-golgi network-proximal CTLA-4 vesicles for surface expression
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2014-04-01
Year available 2014
Sub-type Article (original research)
DOI 10.1128/MCB.01331-13
Open Access Status DOI
Volume 34
Issue 8
Start page 1486
End page 1499
Total pages 14
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted 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 promotedthe 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/Rab8effector complex in the transport of CTLA-4 to the surfaces of T cells.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
UQ Diamantina Institute - Open Access Collection
 
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