Two Rab2 interactors regulate dense-core vesicle maturation.
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.
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.
Michael
M
Ailion
European Neuroscience Institute, 37077 Göttingen, Germany; International Max Planck Research School Molecular Biology, 37077 Göttingen, Germany.
Mandy
M
Hannemann
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Susan
S
Dalton
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Andrea
A
Pappas
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Shigeki
S
Watanabe
European Neuroscience Institute, 37077 Göttingen, Germany; DFG research Center for Molecular Physiology of the Brain (CMPB), 37077 Göttingen, Germany.
Jan
J
Hegermann
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Qiang
Q
Liu
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Hsiao-Fen
HF
Han
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Mingyu
M
Gu
Department of Biochemistry, University of Washington, Seattle WA, 98195, USA.
Morgan Q
MQ
Goulding
European Neuroscience Institute, 37077 Göttingen, Germany.
Nikhil
N
Sasidharan
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Kim
K
Schuske
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
Patrick
P
Hullett
European Neuroscience Institute, 37077 Göttingen, Germany; DFG research Center for Molecular Physiology of the Brain (CMPB), 37077 Göttingen, Germany.
Stefan
S
Eimer
Howard Hughes Medical Institute, Department of Biology, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: jorgensen@biology.utah.edu.
Erik M
EM
Jorgensen
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D021381:Protein Transport; D022142:Secretory Vesicles / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D020693:rab2 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D049452:Green Fluorescent Proteins; D020693:rab2 GTP-Binding Protein