Author:
Bassaganyas Laia,Popa Stephanie J.,Horlbeck Max,Ashok Anupama,Stewart Sarah E.,Butnaru Cristian M.,Brouwers Nathalie,Heydari Kartoosh,Ripoche Jean,Weissman Jonathan,Schekman Randy,Malhotra Vivek,Moreau Kevin,Villeneuve Julien
Abstract
AbstractProtein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathways function remains incomplete, and mechanisms involved in their adaptation poorly understood. Here, we present a powerful strategy based on a pooled genome-wide CRISPRi screen that allowed the identification of new factors involved in protein transport. Two newly identified factors, TTC17 and CCDC157, localized along the secretory pathway and were found to interact with resident proteins of ER-Golgi membranes. In addition, we uncovered that upon TTC17 knockdown, the polarized organization of Golgi cisternae was altered, creating glycosylation defects, and that CCDC157 is an important factor for the fusion of transport carriers to the Golgi complex. In conclusion, our work identified and characterized new actors in the mechanisms of protein transport and secretion, and opens stimulating perspectives for the use of our platform in physiological and pathological contexts.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
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