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The dense‐core vesicle maturation protein CCCP ‐1 binds RAB ‐2 and membranes through its C‐terminal domain
Author(s) -
CattinOrtolá Jérôme,
Topalidou Irini,
Dosey Annie,
Merz Alexey J.,
Ailion Michael
Publication year - 2017
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12507
Subject(s) - rab , biology , biogenesis , microbiology and biotechnology , vesicle , golgi apparatus , gtpase , coiled coil , organelle , vesicular transport protein , small gtpase , caenorhabditis elegans , biochemistry , endoplasmic reticulum , membrane , signal transduction , gene
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 Caenorhabditis 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. In addition, 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.