PT  - JOURNAL ARTICLE
AU  - Jérôme Cattin-Ortolá
AU  - Irini Topalidou
AU  - Annie Dosey
AU  - Alexey J. Merz
AU  - Michael Ailion
TI  - The Dense-Core Vesicle Maturation Protein CCCP-1 Binds both RAB-2 and Membranes through a Conserved C-terminal Coiled-coil Domain
AID  - 10.1101/105668
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 105668
4099  - http://biorxiv.org/content/early/2017/02/03/105668.short
4100  - http://biorxiv.org/content/early/2017/02/03/105668.full
AB  - Dense-core vesicles (DCVs) are secretory organelles that store and release modulatory neurotransmitters from neurons and endocrine cells. Recently, the conserved coiled-coil protein CCCP-1 was identified as a component of the DCV biogenesis pathway in the nematode C. elegans. CCCP-1 binds the small GTPase RAB-2 and colocalizes with it at the trans-Golgi. Here we report a structure-function analysis of CCCP-1 to identify domains of the protein important for its localization, binding to RAB-2, and function in DCV biogenesis. We find that the CCCP-1 C-terminal domain (CC3) has multiple activities. CC3 is necessary and sufficient for CCCP-1 localization to the trans-Golgi and for binding to RAB-2, and is required for the function of CCCP-1 in DCV biogenesis. Additionally, CCCP-1 binds membranes directly through its CC3 domain, indicating that CC3 comprises a previously uncharacterized lipid-binding motif. We conclude that CCCP-1 is a coiled-coil protein that binds an activated Rab and localizes to the Golgi via its C-terminus, properties similar to members of the golgin family of proteins. Consistent with this idea, CCCP-1 also shares biophysical features with golgins.