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
Subject 1312 Molecular Biology
1307 Cell Biology
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.
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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