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.
European Neuroscience Institute, 37077 Göttingen, Germany; International Max Planck Research School Molecular Biology, 37077 Göttingen, Germany.
Neuron. 2014 Apr 2;82(1):167-80. doi: 10.1016/j.neuron.2014.02.017.
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.
致密核心囊泡。致密核心囊泡在高尔基体内产生，然后在成熟过程中分拣货物，然后再分泌。为了鉴定在这条途径中起作用的蛋白质，我们在秀丽隐杆线虫中进行了遗传筛选，以寻找在致密核心囊泡功能上有缺陷的突变体。我们鉴定了两种保守的 Rab2 结合蛋白：RUND-1，一种 RUN 结构域蛋白，和 CCCP-1，一种卷曲螺旋蛋白。RUND-1 和 CCCP-1 在高尔基体内与 RAB-2 共定位，rab-2、rund-1 和 cccp-1 突变体在可溶性和跨膜致密核心囊泡货物的分拣中具有相似的缺陷。RUND-1 还与 Rab2 GAP 蛋白 TBC-8 和 BAR 结构域蛋白 RIC-19 相互作用，后者是 RAB-2 的效应物。总之，一个保守蛋白途径控制着高尔基体内致密核心囊泡的成熟。
