Two Rab2 interactors regulate dense-core vesicle maturation
02.04.2014
Ailion M, Hannemann M, Dalton S, Pappas A, Watanabe S, Hegermann J, Liu Q, Han HF, Gu M, Goulding MQ, Sasidharan N, Schuske K, Hullett P, Eimer S, Jorgensen EM.
Neuron. 2014;82(1):167-80.
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.
