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UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans

¹ European Neuroscience Institute Goettingen, German Research Foundation Research Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany
² Functional Genomics and Proteomics Unit, Biology Department, Catholic University of Leuven, BE-3000 Leuven, Belgium
³ Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607

Correspondence to Stefan Eimer: seimer{at}gwdg.de

Small guanosine triphosphatases of the Rab family regulate intracellular vesicular trafficking. Rab2 is highly expressed in the nervous system, yet its function in neurons is unknown. In Caenorhabditis elegans, unc-108/rab-2 mutants have been isolated based on their locomotory defects. We show that the locomotion defects of rab-2 mutants are not caused by defects in synaptic vesicle release but by defects in dense core vesicle (DCV) signaling. DCVs in rab-2 mutants are often enlarged and heterogeneous in size; however, their number and distribution are not affected. This implicates Rab2 in the biogenesis of DCVs at the Golgi complex. We demonstrate that Rab2 is required to prevent DCV cargo from inappropriately entering late endosomal compartments during DCV maturation. Finally, we show that RIC-19, the C. elegans orthologue of the human diabetes autoantigen ICA69, is also involved in DCV maturation and is recruited to Golgi membranes by activated RAB-2. Thus, we propose that RAB-2 and its effector RIC-19 are required for neuronal DCV maturation.

Abbreviations used in this paper: ACh, acetylcholine; DCV, dense core vesicle; DNC, dorsal nerve cord; GPCR, G protein–coupled receptor; HPF, high pressure freeze; HSN, hermaphrodite-specific neuron; iDCV, immature DCV; MALDI-TOF MS, matrix-assisted laser desorption ionization time of flight mass spectrometry; mDCV, mature DCV; NGM, Nematode growth medium; NMJ, neuromuscular junction; SV, synaptic vesicle; TFA, trifluoroacetic acid; VNC, ventral nerve cord.

© 2009 Sumakovic et al.
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This article has been cited by other articles:

• Short, B. (2009). Rab2 directs a stop-loss program. JCB 186: 769-769 [Full Text]  
• Edwards, S. L., Charlie, N. K., Richmond, J. E., Hegermann, J., Eimer, S., Miller, K. G. (2009). Impaired dense core vesicle maturation in Caenorhabditis elegans mutants lacking Rab2. JCB 186: 881-895 [Abstract] [Full Text]  

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