The Dense ‐Core Vesicle Maturation Protein CCCP‐1 Binds RAB‐2 and Membranes through its C‐terminal Domain

Abstract
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 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 may comprise 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. CCCP‐1 also shares biophysical features with golgins; it has an elongated shape and forms oligomers.

Synopsis statement
CCCP‐1 is a coiled‐coil protein important for dense‐core vesicle (DCV) biogenesis. A structure‐function analysis of CCCP‐1 shows that its C‐terminal domain is required for (1) localization to membrane compartments near the trans‐...

Source: Traffic - July 29, 2017 Category: Research Authors: J érôme Cattin‐Ortolá, Irini Topalidou, Annie Dosey, Alexey J. Merz, Michael Ailion Tags: ORIGINAL ARTICLE Source Type: research