Parkinson, K;
Baines, AE;
Keller, T;
Gruenheit, N;
Bragg, L;
North, RA;
Thompson, CRL;
(2014)
Calcium-dependent regulation of Rab activation and vesicle fusion by an intracellular P2X ion channel.
Nature Cell Biology
, 16
pp. 87-98.
10.1038/ncb2887.
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Calcium-dependent regulation of Rab activation and vesicle fusion by an intracellular P2X ion channel.pdf - Accepted Version Download (6MB) | Preview |
Abstract
Rab GTPases play key roles in the delivery, docking and fusion of intracellular vesicles. However, the mechanism by which spatial and temporal regulation of Rab GTPase activity is controlled is poorly understood. Here we describe a mechanism by which localized calcium release through a vesicular ion channel controls Rab GTPase activity. We show that activation of P2XA, an intracellular ion channel localized to the Dictyostelium discoideum contractile vacuole system, results in calcium efflux required for downregulation of Rab11a activity and efficient vacuole fusion. Vacuole fusion and Rab11a downregulation require the activity of CnrF, an EF-hand-containing Rab GAP found in a complex with Rab11a and P2XA. CnrF Rab GAP activity for Rab11a is enhanced by the presence of calcium and the EF-hand domain. These findings suggest that P2XA activation results in vacuolar calcium release, which triggers activation of CnrF Rab GAP activity and subsequent downregulation of Rab11a to allow vacuole fusion.
Type: | Article |
---|---|
Title: | Calcium-dependent regulation of Rab activation and vesicle fusion by an intracellular P2X ion channel |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1038/ncb2887 |
Publisher version: | https://doi.org/10.1038/ncb2887 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Calcium signalling, Dictyostelium discoideum, Membrane trafficking |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
URI: | https://discovery.ucl.ac.uk/id/eprint/10089745 |
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