CCDC186 recruits EARP and controls dense-core vesicle cargo sorting by exit

Cattin-Ortola, J.; Topalidou, I.; Lau, H.-T.; Hummer, B.; Asensio, C. S.; Ong, S.-E.; Ailion, M.

doi:10.1101/616458

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bioRxiv · 10.1101/616458

CCDC186 recruits EARP and controls dense-core vesicle cargo sorting by exit

Cattin-Ortola, J.·Topalidou, I.·Lau, H.-T.·Hummer, B.·Asensio, C. S.·Ong, S.-E.·Ailion, M.

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Abstract

The regulated release of peptide hormones depends on their packaging into dense-core vesicles (DCVs). Two models have been proposed for DCV cargo sorting. The \"sorting by entry\" model proposes that DCV cargos selectively enter nascent DCVs at the trans-Golgi network (TGN). The \"sorting by exit\" model proposes that sorting occurs by the post-TGN removal of non-DCV cargos and retention of mature DCV cargos. Here we show that the coiled-coil protein CCDC186 controls sorting by exit. Ccdc186 KO insulinoma cells secrete less insulin, fail to retain insulin and carboxypeptidase E in mature DCVs at the cell periphery, and fail to remove carboxypeptidase D from immature DCVs. A mutation affecting the endosome-associated recycling protein (EARP) complex causes similar defects in DCV cargo retention and removal. CCDC186 and EARP may act together to control the post-Golgi retention of cargos in mature DCVs.

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Cattin-Ortola, J., Topalidou, I., Lau, H.-T., Hummer, B., Asensio, C. S., Ong, S.-E., Ailion, M.. 2019-04-23. CCDC186 recruits EARP and controls dense-core vesicle cargo sorting by exit. https://doi.org/10.1101/616458

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