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PMID: 19797081 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of cell biology ·Vol. 186 ·No. 6 ·2009-09-21 ·Pages 897-914

Sumakovic M, Hegermann J, Luo L, Husson SJ, Schwarze K, Olendrowitz C, Schoofs L, Richmond J, Eimer S

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Autoantigens/genetics,metabolism Caenorhabditis elegans/enzymology,genetics,ultrastructure Caenorhabditis elegans Proteins/chemistry,genetics,metabolism Endosomes/enzymology Enzyme Stability Genotype Golgi Apparatus/enzymology Guanosine Triphosphate/metabolism Humans Hydrolysis Kinetics Locomotion Models, Molecular Molecular Sequence Data Mutation Neuromuscular Junction/enzymology Neurons/enzymology,ultrastructure Neuropeptides/metabolism Phenotype Protein Conformation Protein Transport Secretory Vesicles/enzymology,ultrastructure Synapses/enzymology Synaptic Vesicles/metabolism rab GTP-Binding Proteins/chemistry,genetics,metabolism rab2 GTP-Binding Protein/chemistry,genetics,metabolism
Chemicals
Autoantigens Caenorhabditis elegans Proteins Neuropeptides ric-19 protein, C elegans Guanosine Triphosphate UNC-108 protein, C elegans rab GTP-Binding Proteins rab2 GTP-Binding Protein
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sumakovic Marija
European Neuroscience Institute Goettingen, German Research Foundation Research Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany.
Hegermann Jan
Luo Ling
Husson Steven J
Schwarze Katrin
Olendrowitz Christian
Schoofs Liliane
Richmond Janet
Eimer Stefan
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.200902096
Published
2009-09-21
Pages
897-914
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2753160
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.200902096 PMC Full Text View journal details
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