Abstract
Peptide neuromodulators are released from a unique organelle: the dense-core vesicle. Dense-core vesicles are generated at the trans-Golgi and then sort cargo during maturation before being secreted. To identify proteins that act in this pathway, we performed a genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We identified two conserved Rab2-binding proteins: RUND-1, a RUN domain protein, and CCCP-1, a coiled-coil protein. RUND-1 and CCCP-1 colocalize with RAB-2 at the Golgi, and rab-2, rund-1, and cccp-1 mutants have similar defects in sorting soluble and transmembrane dense-core vesicle cargos. RUND-1 also interacts with the Rab2 GAP protein TBC-8 and the BAR domain protein RIC-19, a RAB-2 effector. In summary, a pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network.
Copyright © 2014 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Analysis of Variance
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Animals
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Animals, Genetically Modified
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Caenorhabditis elegans
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Chromosome Mapping
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Cloning, Molecular
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Endosomes / metabolism
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Endosomes / ultrastructure
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Golgi Apparatus / metabolism
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Golgi Apparatus / ultrastructure
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Microscopy, Electron, Transmission
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Molecular Sequence Data
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Mutation / genetics*
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Protein Transport
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Secretory Vesicles / genetics
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Secretory Vesicles / metabolism*
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Secretory Vesicles / ultrastructure
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rab2 GTP-Binding Protein / genetics
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rab2 GTP-Binding Protein / metabolism*
Substances
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Caenorhabditis elegans Proteins
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Green Fluorescent Proteins
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rab2 GTP-Binding Protein
Associated data
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GENBANK/JN986879
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GENBANK/JN986880