Genome-wide CRISPR screening identifies new regulators of glycoprotein secretion

全基因组 CRISPR 筛选鉴定出新的糖蛋白分泌调节剂

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作者:Stephanie Popa, Julien Villeneuve, Sarah Stewart, Esther Perez Garcia, Anna Petrunkina Harrison, Kevin Moreau

Background

The fundamental process of protein secretion from eukaryotic cells has been well described for many years, yet gaps in our understanding of how this process is regulated remain.

Conclusions

This study has identified new factors for protein secretion involved in Golgi homeostasis.

Methods

With the aim of identifying novel genes involved in the secretion of glycoproteins, we used a screening pipeline consisting of a pooled genome-wide CRISPR screen, followed by secondary siRNA screening of the hits to identify and validate several novel regulators of protein secretion.

Results

We present approximately 50 novel genes not previously associated with protein secretion, many of which also had an effect on the structure of the Golgi apparatus. We further studied a small selection of hits to investigate their subcellular localisation. One of these, GPR161, is a novel Golgi-resident protein that we propose maintains Golgi structure via an interaction with golgin A5. Conclusions: This study has identified new factors for protein secretion involved in Golgi homeostasis.

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