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Abstract

COPI vesicles mediate retrograde Golgi to ER transport and intra-Golgi transport within the secretory pathway. COPI vesicles are Golgi derived vesicles, which are coated with heptameric complex known as coatomer. Coatomer is made up of seven subunits alpha, beta, beta prime,delta, gamma,zeta and epsilon-COP. COPI coatomer is recruited to the Golgi membrane with the help of small GTPases Arf to stimulate the vesicle formation and capture cargo proteins to deliver them to the targeted membrane.

In mammals the -COP subunit has two paralogs. Whereas in the related COPII system, paralogs of coat subunits were shown to expand the cargo repertoire of COPII vesicles, no paralog specific function had been described to date for COPI paralog subunits. In this work we have set out to investigate such specific functions.

Guided by RNAseq data in differentiating mES that showed that Copg1 is upregulated during neuronal differentiation. We generated Copg1 and Copg2 KO P19 pluripotent cells and studied if they could differentiate. Strikingly Copg1 KO cells fail to form tight embryonic bodies (EBs) and to form long neurites though they could differentiate into neurons.

This work shows for the first time strong evidence for paralog-specific function of the COPI pathway in mammalian cells.