A network of cytosolic factors targets SRP-independent proteins to the endoplasmic reticulum.

Tslil Ast, Galit Cohen, Maya Schuldiner

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.

Cell 2013 Feb 28

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Translocation into the endoplasmic reticulum (ER) is an initial and crucial biogenesis step for all secreted and endomembrane proteins in eukaryotes. ER insertion can take place through the well-characterized signal recognition particle (SRP)-dependent pathway or the less-studied route of SRP-independent translocation. To better understand the prevalence of the SRP-independent pathway, we systematically defined the translocational dependence of the yeast secretome. By combining hydropathy-based analysis and microscopy, we uncovered that a previously unappreciated fraction of the yeast secretome translocates without the aid of the SRP. Furthermore, we validated a family of SRP-independent substrates-the glycosylphosphatidylinositol (GPI)-anchored proteins. Studying this family, we identified a determinant for ER targeting and uncovered a network of cytosolic proteins that facilitate SRP-independent targeting and translocation. These findings highlight the underappreciated complexity of SRP-independent translocation, which enables this pathway to efficiently cope with its extensive substrate flux. Copyright © 2013 Elsevier Inc. All rights reserved.

Citation

Tslil Ast, Galit Cohen, Maya Schuldiner. A network of cytosolic factors targets SRP-independent proteins to the endoplasmic reticulum. Cell. 2013 Feb 28;152(5):1134-45