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

• Published in: The EMBO journal Vol. 18; no. 6; pp. 1506 - 1515
• Main Authors: Kochendorfer, K.U, Then, A.R, Kearns, B.G, Bankaitis, V.A, Mayinger, P
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 15.03.1999; Blackwell Publishing Ltd
• Subjects: active transport; adenosine triphosphate; Adenosine Triphosphate - metabolism; Amino Acid Sequence; Base Sequence; carboxypeptidases; cell membranes; endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Fungal Proteins - chemistry; Fungal Proteins - genetics; Fungal Proteins - metabolism; Golgi Apparatus - metabolism; inositol; Kinetics; Liposomes - metabolism; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; microsomal ATP transport; microsomes; Microsomes - metabolism; molecular conformation; Molecular Sequence Data; mutants; phenotype; phospholipid metabolism; Phospholipids - metabolism; Phosphoric Monoester Hydrolases; protein folding; protein trafficking; protein transport; proteins; Proteolipids - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Sac1p; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; serine-type carboxypeptidases
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1093/emboj/18.6.1506

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 sac1Δ microsomal extracts, but is unable to catalyze ATP transport itself. In addition, we demonstrate that sac1Δ 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.