In a study published in Journal of Cell Science, the Moreau lab used a CRISPR screen to identify regulators of Galectin secretion and show the benefit of such approach to study unconventional secretion.
Eukaryotic cells have a highly evolved system of protein secretion, and dysfunction in this pathway has been associated with several diseases including cancer, infection, metabolic disease and neurological disorders. Most proteins are secreted using the endoplasmic reticulum (ER)/Golgi network. However, several cytosolic proteins are secreted by unconventional transport pathways. These include members of the annexins, heat shock proteins, interleukins, fibroblast growth factors, galectins, and more recently misfolded proteins. The extracellular functions of these proteins and their associations to several diseases due to perturbations in their secretion are well documented. However, the mechanism of secretion and its regulation remain largely uncharacterised. This represents a major gap in our understanding of the fundamental mechanisms supporting protein trafficking and secretion.
The study describes the benefits of using a genome-wide screen using CRISPR/Cas9 technology to identify new regulators of unconventional secretion. Several hits involved in regulating the secretion of galectins are validated using this approach. It also addresses a controversy in the field regarding the role of the glycosylation pathway and the role of extracellular vesicles in galectin secretion.
The authors aim to build on this research by validating other hits in order to fully understand the mechanisms of unconventional secretion.