Two Rab2 Interactors Regulate Dense-Core Vesicle Maturation

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• 作者：Michael Ailion¹ ; ² ; ^{mailion@uw.edu" class="auth_mail} ; Mandy Hannemann³ ; ⁴ ; Susan Dalton¹ ; Andrea Pappas¹ ; Shigeki Watanabe¹ ; Jan Hegermann³ ; ⁵ ; ⁶ ; Qiang Liu¹ ; Hsiao-Fen Han¹ ; Mingyu Gu¹ ; Morgan Q. Goulding² ; Nikhil Sasidharan³ ; Kim Schuske¹ ; Patrick Hullett¹ ; Stefan Eimer³ ; ⁵ ; Erik M. Jorgensen¹ ; ^{jorgensen@biology.utah.edu" class="auth_mail}
• 刊名：Neuron
• 出版年：2 April, 2014
• 年：2014
• 卷：82
• 期：1
• 页码：167-180
• 全文大小：2885 K

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Summary

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.