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Neuron. 2014 Apr 2;82(1):167-80. doi: 10.1016/j.neuron.2014.02.017.

Two Rab2 interactors regulate dense-core vesicle maturation.

Author information

1
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA; Department of Biochemistry, University of Washington, Seattle WA, 98195, USA. Electronic address: mailion@uw.edu.
2
European Neuroscience Institute, 37077 Göttingen, Germany; International Max Planck Research School Molecular Biology, 37077 Göttingen, Germany.
3
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
4
European Neuroscience Institute, 37077 Göttingen, Germany; DFG research Center for Molecular Physiology of the Brain (CMPB), 37077 Göttingen, Germany.
5
Department of Biochemistry, University of Washington, Seattle WA, 98195, USA.
6
European Neuroscience Institute, 37077 Göttingen, Germany.
7
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jorgensen@biology.utah.edu.

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.

PMID:
24698274
PMCID:
PMC3997996
DOI:
10.1016/j.neuron.2014.02.017
[Indexed for MEDLINE]
Free PMC Article

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