Macromolecular assemblies regulate nonvesicular phosphatidylserine traffic in yeast.
PtdSer (phosphatidylserine) is synthesized in the endoplasmic reticulum and the related MAM (mitochondria-associated membrane), and transported to the PtdSer decarboxylases, Pds1p in the mitochondria, and Psd2p in the Golgi. Genetic and biochemical analyses of PtdSer transport are now revealing the role of specific protein and lipid assemblies on different organelles that regulate non-vesicular PtdSer transport. The transport of PtdSer from MAM to mitochondria is regulated by at least three genes: MET30 (encoding a ubiquitin ligase), MET4 (encoding a transcription factor), and one or more unknown genes whose transcription is regulated by MET4. MET30-dependent ubiquitination is required for the MAM to function as a competent donor membrane and for the mitochondria to function as a competent acceptor membrane. Non-vesicular transport of PtdSer to the locus of Psd2p is under the control of at least three genes, STT4 [encoding Stt4p (phosphatidylinositol 4-kinase)], PSTB2 (encoding the lipid-binding protein PstB2p) and PSD2 (encoding Psd2p). Stt4p is proposed to produce a pool of PtdIns4P that is necessary for lipid transport. PstB2p and Psd2p must be present on the acceptor membrane for PtdSer transport to occur. Psd2p contains a C2 (Ca(2+) and phospholipid binding sequence) domain that is required for lipid transport. Reconstitution studies with chemically defined donor membranes demonstrate that membrane domains rich in the anionic lipids, PtdSer, PtdIns4P and phosphatidic acid function as the most efficient donors of PtdSer to Psd2p. The emerging view is that macromolecular complexes dependent on protein-protein and protein-lipid interactions form between donor and acceptor membranes and serve to dock the compartments and facilitate phospholipid transport.
Choi
J-Y
JY
Program in Cell Biology, Department of Medicine, National Jewish Medical and Research Center, Denver, CO, USA.
Riekhof
W R
WR
Wu
W-I
WI
Voelker
D R
DR
D001693:Biological Transport, Active; D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism*; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D022161:Transport Vesicles
D046911:Macromolecular Substances; D010718:Phosphatidylserines