UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans.
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.
European Neuroscience Institute Goettingen, German Research Foundation Research Center for Molecular Physiology of the Brain, 37077 Goettingen, Germany.
Marija
M
Sumakovic
Jan
J
Hegermann
Ling
L
Luo
Steven J
SJ
Husson
Katrin
K
Schwarze
Christian
C
Olendrowitz
Liliane
L
Schoofs
Janet
J
Richmond
Stefan
S
Eimer
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011992:Endosomes / Q000201:enzymology; D004795:Enzyme Stability; D005838:Genotype; D006056:Golgi Apparatus / Q000201:enzymology; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D008124:Locomotion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009469:Neuromuscular Junction / Q000201:enzymology; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000378:metabolism; D010641:Phenotype; D011487:Protein Conformation; D021381:Protein Transport; D022142:Secretory Vesicles / Q000201:enzymology* / Q000648:ultrastructure; D013569:Synapses / Q000201:enzymology; D013572:Synaptic Vesicles / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020693:rab2 GTP-Binding Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D001324:Autoantigens; D029742:Caenorhabditis elegans Proteins; D009479:Neuropeptides; C490186:ric-19 protein, C elegans; D006160:Guanosine Triphosphate; C534960:UNC-108 protein, C elegans; D020691:rab GTP-Binding Proteins; D020693:rab2 GTP-Binding Protein