title: Remodeling of secretory compartments creates CUPS during nutrient starvation.
abstract: Upon starvation, Grh1, a peripheral membrane protein located at endoplasmic reticulum (ER) exit sites and early Golgi in Saccharomyces cerevisiae under growth conditions, relocates to a compartment called compartment for unconventional protein secretion (CUPS). Here we report that CUPS lack Golgi enzymes, but contain the coat protein complex II (COPII) vesicle tethering protein Uso1 and the Golgi t-SNARE Sed5. Interestingly, CUPS biogenesis is independent of COPII- and COPI-mediated membrane transport. Pik1- and Sec7-mediated membrane export from the late Golgi is required for complete assembly of CUPS, and Vps34 is needed for their maintenance. CUPS formation is triggered by glucose, but not nitrogen starvation. Moreover, upon return to growth conditions, CUPS are absorbed into the ER, and not the vacuole. Altogether our findings indicate that CUPS are not specialized autophagosomes as suggested previously. We suggest that starvation triggers relocation of secretory and endosomal membranes, but not their enzymes, to generate CUPS to sort and secrete proteins that do not enter, or are not processed by enzymes of the ER-Golgi pathway of secretion.
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Cruz-Garcia
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Curwin
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Popoff
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bruns
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Duran
authors.affiliation: Cell and Developmental Biology Programme, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain Universitat Pompeu Fabra (UPF), 08002 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain vivek.malhotra@crg.eu.
authors.forename: Vivek
authors.initials: V
authors.lastname: Malhotra
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D022181:COP-Coated Vesicles / Q000378:metabolism*; D058546:Class III Phosphatidylinositol 3-Kinases / Q000378:metabolism; D003470:Culture Media; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D003470:Culture Media; C554600:Grh1 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; D050765:Qa-SNARE Proteins; D029701:Saccharomyces cerevisiae Proteins; C066755:Sec7 guanine nucleotide exchange factors; C077554:Sed5 protein, S cerevisiae; C086888:USO1 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D058546:Class III Phosphatidylinositol 3-Kinases; D019870:1-Phosphatidylinositol 4-Kinase; C441760:PIK1 protein, S cerevisiae; D005947:Glucose