title: A network of cytosolic factors targets SRP-independent proteins to the endoplasmic reticulum.
abstract: 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.
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Tslil
authors: T
authors: Ast
authors: Galit
authors: G
authors: Cohen
authors: Maya
authors: M
authors: Schuldiner
mesh_terms: D003600:Cytosol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D018832:Molecular Chaperones / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D018271:Signal Recognition Particle / Q000378:metabolism
chemical_list: D017261:Glycosylphosphatidylinositols; D050956:HSP40 Heat-Shock Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D018271:Signal Recognition Particle