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Vol. 17, Issue 6, 2617-2625, June 2006
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*Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110; Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030; and Fukuda Initiative Research Unit, RIKEN, Wako, Saitama 351-0198, Japan
Submitted December 27, 2005;
Revised February 24, 2006;
Accepted March 20, 2006
Monitoring Editor: Francis Barr
Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Michael L. Nonet ( nonetm{at}pcg.wustl.edu)
This article has been cited by other articles:
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  M. J. Merrins and E. L. Stuenkel Kinetics of Rab27a-dependent actions on vesicle docking and priming in pancreatic {beta}-cells J. Physiol., November 15, 2008; 586(22): 5367 - 5381. [Abstract] [Full Text] [PDF]
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 D. Tanaka, K. Kameyama, H. Okamoto, and M. Doi Caenorhabditis elegans Rab escort protein (REP-1) differently regulates each Rab protein function and localization in a tissue-dependent manner Genes Cells, November 1, 2008; 13(11): 1141 - 1157. [Abstract] [Full Text] [PDF]
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 T. R. Mahoney, S. Luo, E. K. Round, M. Brauner, A. Gottschalk, J. H. Thomas, and M. L. Nonet Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans PNAS, October 21, 2008; 105(42): 16350 - 16355. [Abstract] [Full Text] [PDF]
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E. Yu, E. Kanno, S. Choi, M. Sugimori, J. E. Moreira, R. R. Llinas, and M. Fukuda Role of Rab27 in synaptic transmission at the squid giant synapse PNAS, October 14, 2008; 105(41): 16003 - 16008. [Abstract] [Full Text] [PDF]
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 A. C. Figueiredo, C. Wasmeier, A. K. Tarafder, J. S. Ramalho, R. A. Baron, and M. C. Seabra Rab3GEP Is the Non-redundant Guanine Nucleotide Exchange Factor for Rab27a in Melanocytes J. Biol. Chem., August 22, 2008; 283(34): 23209 - 23216. [Abstract] [Full Text] [PDF]
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