Two Rab2 Interactors Regulate Dense-Core Vesicle Maturation

被引:60
作者
Ailion, Michael [1 ,2 ]
Hannemann, Mandy [3 ,4 ]
Dalton, Susan [1 ]
Pappas, Andrea [1 ]
Watanabe, Shigeki [1 ]
Hegermann, Jan [3 ,5 ]
Liu, Qiang [1 ]
Han, Hsiao-Fen [1 ]
Gu, Mingyu [1 ]
Goulding, Morgan Q. [2 ]
Sasidharan, Nikhil [3 ]
Schuske, Kim [1 ]
Hullett, Patrick [1 ]
Eimer, Stefan [3 ,5 ]
Jorgensen, Erik M. [1 ]
机构
[1] Univ Utah, Howard Hughes Med Inst, Dept Biol, Salt Lake City, UT 84112 USA
[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[3] European Neurosci Inst, D-37077 Gottingen, Germany
[4] Int Max Planck Res Sch Mol Biol, D-37077 Gottingen, Germany
[5] DFG Res Ctr Mol Physiol Brain CMPB, D-37077 Gottingen, Germany
关键词
IMMATURE SECRETORY GRANULES; GTP-BINDING-PROTEINS; CAENORHABDITIS-ELEGANS; C-ELEGANS; RUN DOMAIN; RAB6-INTERACTING PROTEIN-1; HOMOTYPIC FUSION; TRANS-GOLGI; UNC-31; CAPS; PC12; CELLS;
D O I
10.1016/j.neuron.2014.02.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 RAB2 effector. In summary, a pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network.
引用
收藏
页码:167 / 180
页数:14
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