Home LiteratureArticle Details
PMID: 10075922 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Sac1p plays a crucial role in microsomal ATP transport, which is distinct from its function in Golgi phospholipid metabolism.

The EMBO journal ·Vol. 18 ·No. 6 ·1999-03-15 ·Pages 1506-15

Kochendörfer KU, Then AR, Kearns BG, Bankaitis VA, Mayinger P

Abstract

Analysis of microsomal ATP transport in yeast resulted in the identification of Sac1p as an important factor in efficient ATP uptake into the endoplasmic reticulum (ER) lumen. Yet it remained unclear whether Sac1p is the authentic transporter in this reaction. Sac1p shows no homology to other known solute transporters but displays similarity to the N-terminal non-catalytic domain of a subset of inositol 5'-phosphatases. Furthermore, Sac1p was demonstrated to be involved in inositol phospholipid metabolism, an activity whose absence contributes to the bypass Sec14p phenotype in sac1 mutants. We now show that purified recombinant Sac1p can complement ATP transport defects when reconstituted together with sac1Delta microsomal extracts, but is unable to catalyze ATP transport itself. In addition, we demonstrate that sac1Delta strains are defective in ER protein translocation and folding, which is a direct consequence of impaired ATP transport function and not related to the role of Sac1p in Golgi inositol phospholipid metabolism. These data suggest that Sac1p is an important regulator of microsomal ATP transport providing a possible link between inositol phospholipid signaling and ATP-dependent processes in the yeast ER.

MeSH Terms
Adenosine Triphosphate/metabolism Amino Acid Sequence Base Sequence Endoplasmic Reticulum/metabolism Fungal Proteins/chemistry,genetics,metabolism Golgi Apparatus/metabolism Kinetics Liposomes/metabolism Membrane Proteins/chemistry,genetics,metabolism Microsomes/metabolism Molecular Sequence Data Phospholipids/metabolism Phosphoric Monoester Hydrolases Proteolipids/metabolism Recombinant Fusion Proteins/chemistry,metabolism Saccharomyces cerevisiae/genetics,growth & development,metabolism Saccharomyces cerevisiae Proteins
Chemicals
Fungal Proteins Liposomes Membrane Proteins Phospholipids Proteolipids Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins proteoliposomes Adenosine Triphosphate SAC1 protein, S cerevisiae Phosphoric Monoester Hydrolases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kochendörfer K U
Zentrum für Molekulare Biologie, Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Then A R
Kearns B G
Bankaitis V A
Mayinger P
References (50)
50 references, click to expand
  1. Sec61p and BiP directly facilitate polypeptide translocation into the ER.
    Cell. 1992 Apr 17;69(2):353-65 PMID: 1568250
  2. Phosphoinositides as regulators in membrane traffic.
    Science. 1996 Mar 15;271(5255):1533-9 PMID: 8599109
  3. Phospholipase D stimulates release of nascent secretory vesicles from the trans-Golgi network.
    J Cell Biol. 1997 Aug 11;138(3):495-504 PMID: 9245781
  4. Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase.
    Cell. 1993 Jun 18;73(6):1197-206 PMID: 8513503
  5. Identification and characterization of an essential family of inositol polyphosphate 5-phosphatases (INP51, INP52 and INP53 gene products) in the yeast Saccharomyces cerevisiae.
    Genetics. 1998 Apr;148(4):1715-29 PMID: 9560389
  6. Secretion in yeast: preprotein binding to a membrane receptor and ATP-dependent translocation are sequential and separable events in vitro.
    J Cell Biol. 1989 Jun;108(6):2101-6 PMID: 2544601
  7. Phospholipid transfer proteins revisited.
    Biochem J. 1997 Jun 1;324 ( Pt 2):353-60 PMID: 9182690
  8. Sac1p of Saccharomyces cerevisiae is not involved in ATP release to the extracellular fluid.
    Biochem Biophys Res Commun. 1997 Jul 9;236(1):50-3 PMID: 9223424
  9. Mutations in the SAC1 gene suppress defects in yeast Golgi and yeast actin function.
    J Cell Biol. 1989 Dec;109(6 Pt 1):2939-50 PMID: 2687291
  10. Essential role for diacylglycerol in protein transport from the yeast Golgi complex.
    Nature. 1997 May 1;387(6628):101-5 PMID: 9139830
  11. The unfolded protein response coordinates the production of endoplasmic reticulum protein and endoplasmic reticulum membrane.
    Mol Biol Cell. 1997 Sep;8(9):1805-14 PMID: 9307975
  12. Cer1p, a novel Hsp70-related protein required for posttranslational endoplasmic reticulum translocation in yeast.
    J Biol Chem. 1996 Nov 29;271(48):30610-3 PMID: 8940034
  13. Transporters of nucleotide sugars, nucleotide sulfate and ATP in the Golgi apparatus.
    Trends Biochem Sci. 1997 Jun;22(6):203-7 PMID: 9204706
  14. Phospholipid transfer proteins: a biological debut.
    Trends Cell Biol. 1991 Jul;1(1):30-4 PMID: 14731807
  15. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
  16. The genetic interaction of kar2 and wbp1 mutations. Distinct functions of binding protein BiP and N-linked glycosylation in the processing pathway of secreted proteins in Saccharomyces cerevisiae.
    Eur J Biochem. 1994 Jun 1;222(2):631-7 PMID: 8020500
  17. Splicing: HACking into the unfolded-protein response.
    Curr Biol. 1998 Feb 12;8(4):R121-3 PMID: 9501974
  18. Suppressors of yeast actin mutations.
    Genetics. 1989 Apr;121(4):659-74 PMID: 2656401
  19. A presynaptic inositol-5-phosphatase.
    Nature. 1996 Jan 25;379(6563):353-7 PMID: 8552192
  20. SAC1p is an integral membrane protein that influences the cellular requirement for phospholipid transfer protein function and inositol in yeast.
    J Cell Biol. 1993 Jul;122(1):79-94 PMID: 8314848
  21. Different subcellular localization of Saccharomyces cerevisiae HMG-CoA reductase isozymes at elevated levels corresponds to distinct endoplasmic reticulum membrane proliferations.
    Mol Biol Cell. 1996 May;7(5):769-89 PMID: 8744950
  22. SSI1 encodes a novel Hsp70 of the Saccharomyces cerevisiae endoplasmic reticulum.
    Mol Cell Biol. 1996 Nov;16(11):6444-56 PMID: 8887673
  23. Binding of secretory precursor polypeptides to a translocon subcomplex is regulated by BiP.
    Cell. 1997 Jan 10;88(1):85-96 PMID: 9019409
  24. S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP.
    Cell. 1989 Jun 30;57(7):1223-36 PMID: 2661019
  25. Translocation of ATP into the lumen of rough endoplasmic reticulum-derived vesicles and its binding to luminal proteins including BiP (GRP 78) and GRP 94.
    J Biol Chem. 1992 Feb 25;267(6):3983-90 PMID: 1740446
  26. An ATP transporter is required for protein translocation into the yeast endoplasmic reticulum.
    EMBO J. 1993 Feb;12(2):659-66 PMID: 8440256
  27. Mixed mechanisms in yeast pre-mRNA splicing?
    Cell. 1996 Nov 1;87(3):357-9 PMID: 8898188
  28. BiP/Kar2p serves as a molecular chaperone during carboxypeptidase Y folding in yeast.
    J Cell Biol. 1995 Jul;130(1):41-9 PMID: 7790376
  29. Secretion in yeast: reconstitution of the translocation and glycosylation of alpha-factor and invertase in a homologous cell-free system.
    Cell. 1986 Feb 28;44(4):619-28 PMID: 3512097
  30. An essential role for a phospholipid transfer protein in yeast Golgi function.
    Nature. 1990 Oct 11;347(6293):561-2 PMID: 2215682
  31. Vectors for the inducible overexpression of glutathione S-transferase fusion proteins in yeast.
    Yeast. 1993 Jul;9(7):715-22 PMID: 8368005
  32. Protein folding in the cell.
    Nature. 1992 Jan 2;355(6355):33-45 PMID: 1731198
  33. Phospholipid metabolism and membrane dynamics.
    Curr Opin Cell Biol. 1996 Aug;8(4):534-41 PMID: 8791444
  34. Inositols do it all.
    Genes Dev. 1996 May 1;10(9):1051-3 PMID: 8654921
  35. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics.
    Methods Enzymol. 1987;154:164-75 PMID: 3323810
  36. Posttranslational protein transport in yeast reconstituted with a purified complex of Sec proteins and Kar2p.
    Cell. 1995 May 19;81(4):561-70 PMID: 7758110
  37. Mutations in the CDP-choline pathway for phospholipid biosynthesis bypass the requirement for an essential phospholipid transfer protein.
    Cell. 1991 Feb 22;64(4):789-800 PMID: 1997207
  38. Inducible membranes in yeast: relation to the unfolded-protein-response pathway.
    Yeast. 1997 Oct;13(13):1211-29 PMID: 9364746
  39. Sac1p mediates the adenosine triphosphate transport into yeast endoplasmic reticulum that is required for protein translocation.
    J Cell Biol. 1995 Dec;131(6 Pt 1):1377-86 PMID: 8522598
  40. Common principles of protein translocation across membranes.
    Science. 1996 Mar 15;271(5255):1519-26 PMID: 8599107
  41. Disruption of three phosphatidylinositol-polyphosphate 5-phosphatase genes from Saccharomyces cerevisiae results in pleiotropic abnormalities of vacuole morphology, cell shape, and osmohomeostasis.
    Eur J Cell Biol. 1997 Dec;74(4):350-60 PMID: 9438131
  42. Coordinate regulation of phospholipid biosynthesis in Saccharomyces cerevisiae: pleiotropically constitutive opi1 mutant.
    J Bacteriol. 1985 Jun;162(3):1135-41 PMID: 3888957
  43. Galactose as a gratuitous inducer of GAL gene expression in yeasts growing on glucose.
    Gene. 1989 Nov 15;83(1):57-64 PMID: 2512199
  44. Transport of adenosine triphosphate into endoplasmic reticulum proteoliposomes.
    Biochemistry. 1995 Apr 25;34(16):5472-6 PMID: 7727405
  45. Evidence that phospholipase D mediates ADP ribosylation factor-dependent formation of Golgi coated vesicles.
    J Cell Biol. 1996 Jul;134(2):295-306 PMID: 8707816
  46. KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene.
    Cell. 1989 Jun 30;57(7):1211-21 PMID: 2661018
  47. The promoter region of the yeast KAR2 (BiP) gene contains a regulatory domain that responds to the presence of unfolded proteins in the endoplasmic reticulum.
    Mol Cell Biol. 1993 Feb;13(2):877-90 PMID: 8423809
  48. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.
    Gene. 1988 Dec 30;74(2):527-34 PMID: 3073106
  49. INP51, a yeast inositol polyphosphate 5-phosphatase required for phosphatidylinositol 4,5-bisphosphate homeostasis and whose absence confers a cold-resistant phenotype.
    J Biol Chem. 1998 May 8;273(19):11852-61 PMID: 9565610
  50. The Hsp70 homologue Lhs1p is involved in a novel function of the yeast endoplasmic reticulum, refolding and stabilization of heat-denatured protein aggregates.
    J Cell Biol. 1997 May 19;137(4):813-24 PMID: 9151684
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.6.1506
Published
1999-03-15
Pages
1506-15
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171239
Subset
IM
Grants
NIGMS NIH HHS · GM44530 · United States
External Links
PubMed source DOI: 10.1093/emboj/18.6.1506 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2