Sanzà, P;
Evans, RD;
Briggs, DA;
Cantero, M;
Montoliu, L;
Patel, S;
Sviderskaya, EV;
Itzen, A;
Figueiredo, AC;
Seabra, MC;
et al.
Sanzà, P; Evans, RD; Briggs, DA; Cantero, M; Montoliu, L; Patel, S; Sviderskaya, EV; Itzen, A; Figueiredo, AC; Seabra, MC; Hume, AN
(2019)
Nucleotide exchange factor Rab3GEP requires DENN and non-DENN elements for activation and targeting of Rab27a.
J Cell Sci, 132 (9).
jcs212035.
ISSN 1477-9137
https://doi.org/10.1242/jcs.212035
SGUL Authors: Sviderskaya, Elena Vladimirovna
Abstract
Rab GTPases are compartment-specific molecular switches that regulate intracellular vesicular transport in eukaryotes. GDP/GTP exchange factors (GEFs) control Rab activation, and current models propose that localised and regulated GEF activity is important in targeting Rabs to specific membranes. Here, we investigated the mechanism of GEF function using the Rab27a GEF, Rab3GEP (also known as MADD), in melanocytes as a model. We show that Rab3GEP-deficient melanocytes (melan-R3GKO) manifest partial disruption of melanosome dispersion, a read-out of Rab27a activation and targeting. Using rescue of melanosome dispersion in melan-R3GKO cells and effector pull-down approaches we show that the DENN domain of Rab3GEP (conserved among RabGEFs) is necessary, but insufficient, for its cellular function and GEF activity. Finally, using a mitochondrial re-targeting strategy, we show that Rab3GEP can target Rab27a to specific membranes in a GEF-dependent manner. We conclude that Rab3GEP facilitates the activation and targeting of Rab27a to specific membranes, but that it differs from other DENN-containing RabGEFs in requiring DENN and non-DENN elements for both of these activities and by lacking compartment-specific localisation.
Item Type: |
Article
|
Additional Information: |
© 2019. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/4.0This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
Keywords: |
Guanine nucleotide exchange factor, MADD, Melanocyte, Organelle transport, Rab27a, Rab3GEP, 06 Biological Sciences, 11 Medical And Health Sciences, Developmental Biology |
SGUL Research Institute / Research Centre: |
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) |
Journal or Publication Title: |
J Cell Sci |
ISSN: |
1477-9137 |
Language: |
eng |
Dates: |
Date | Event |
---|
30 April 2019 | Published | 21 March 2019 | Published Online | 11 March 2019 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
30898842 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/110890 |
Publisher's version: |
https://doi.org/10.1242/jcs.212035 |
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