HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 34, 23209-23216, August 22, 2008

This Article Free via Author's Choice: AC AC Full Text Full Text (PDF) AC All Versions of this Article: 283/34/23209    most recent M804134200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Figueiredo, A. C. Articles by Seabra, M. C. Search for Related Content PubMed PubMed Citation Articles by Figueiredo, A. C. Articles by Seabra, M. C. Social Bookmarking                      What's this?

Rab3GEP Is the Non-redundant Guanine Nucleotide Exchange Factor for Rab27a in Melanocytes^*

Ana C. Figueiredo¹, Christina Wasmeier, Abul K. Tarafder, José S. Ramalho, Rudi A. Baron, and Miguel C. Seabra²

From the Molecular Medicine, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom and the Centre of Ophthalmology, Biomedical Institute for Research in Light and Image, University of Coimbra, 3004-548 Coimbra, Portugal

Rab GTPases regulate discrete steps in vesicular transport pathways. Rabs require activation by specific guanine nucleotide exchange factors (GEFs) that stimulate the exchange of GDP for GTP. Rab27a controls motility and regulated exocytosis of secretory granules and related organelles. In melanocytes, Rab27a regulates peripheral transport of mature melanosomes by recruiting melanophilin and myosin Va. Here, we studied the activation of Rab27a in melanocytes. We identify Rab3GEP, previously isolated as a GEF for Rab3a, as the non-redundant Rab27a GEF. Similar to Rab27a-deficient ashen melanocytes, Rab3GEP-depleted cells show both clustering of melanosomes in the perinuclear area and loss of the Rab27a effector Mlph. Consistent with a role as an activator, levels of Rab27a-GTP are decreased in cells lacking Rab3GEP. Recombinant Rab3GEP exhibits guanine nucleotide exchange activity against Rab27a and Rab27b in vitro, in addition to its previously documented activity against Rab3. Our results indicate promiscuity in Rab GEF action and suggest that members of related but functionally distinct Rab subfamilies can be controlled by common activators.

Received for publication, May 29, 2008

^* This work was supported by the Wellcome Trust. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Author's Choice—Final version full access.

¹ Supported by a Ph.D. studentship from the Foundation for Science and Technology, Portugal.

Author's Choice

Creative Commons Attribution Non-Commercial License applies to Author Choice Articles

² To whom correspondence should be addressed. E-mail: m.seabra{at}imperial.ac.uk.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				T. D. Nightingale, K. Pattni, A. N. Hume, M. C. Seabra, and D. F. Cutler Rab27a and MyRIP regulate the amount and multimeric state of VWF released from endothelial cells Blood, May 14, 2009; 113(20): 5010 - 5018. [Abstract] [Full Text] [PDF]

				J. A. Williams, X. Chen, and M. E. Sabbatini Small G proteins as key regulators of pancreatic digestive enzyme secretion Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E405 - E414. [Abstract] [Full Text] [PDF]