The medial-Golgi ion pump Pmr1 supplies the yeast secretory pathway with Ca2+ and Mn2+ required for glycosylation, sorting, and endoplasmic reticulum-associated protein degradation.
The yeast Ca2+ adenosine triphosphatase Pmr1, located in medial-Golgi, has been implicated in intracellular transport of Ca2+ and Mn2+ ions. We show here that addition of Mn2+ greatly alleviates defects of pmr1 mutants in N-linked and O-linked protein glycosylation. In contrast, accurate sorting of carboxypeptidase Y (CpY) to the vacuole requires a sufficient supply of intralumenal Ca2+. Most remarkably, pmr1 mutants are also unable to degrade CpY*, a misfolded soluble endoplasmic reticulum protein, and display phenotypes similar to mutants defective in the stress response to malfolded endoplasmic reticulum proteins. Growth inhibition of pmr1 mutants on Ca2+-deficient media is overcome by expression of other Ca2+ pumps, including a SERCA-type Ca2+ adenosine triphosphatase from rabbit, or by Vps10, a sorting receptor guiding non-native luminal proteins to the vacuole. Our analysis corroborates the dual function of Pmr1 in Ca2+ and Mn2+ transport and establishes a novel role of this secretory pathway pump in endoplasmic reticulum-associated processes.
Dürr
G
G
Institut für Biochemie der Universität Stuttgart, D-70569 Stuttgart, Germany.
Strayle
J
J
Plemper
R
R
Elbs
S
S
Klee
S K
SK
Catty
P
P
Wolf
D H
DH
Rudolph
H K
HK
D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D002413:Cations, Divalent; D003470:Culture Media; D004533:Egtazic Acid; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000201:enzymology*; D008345:Manganese / Q000378:metabolism*; D010641:Phenotype; D053499:Plasma Membrane Calcium-Transporting ATPases; D011956:Receptors, Cell Surface / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development; D029701:Saccharomyces cerevisiae Proteins; D014617:Vacuoles; D033921:Vesicular Transport Proteins
D002413:Cations, Divalent; D003470:Culture Media; D005656:Fungal Proteins; C087335:PEP1 protein, S cerevisiae; C085484:PMC1 protein, S cerevisiae; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D008345:Manganese; D004533:Egtazic Acid; D053499:Plasma Membrane Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium