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Macromolecular Assemblies of Lipids and Proteins Regulate Non‐Vesicular Phospholipid Traffic
Author(s) -
Voelker Dennis R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a38-a
Subject(s) - microbiology and biotechnology , golgi apparatus , ubiquitin ligase , transport protein , phosphatidic acid , protein subunit , ubiquitin , biology , organelle , biochemistry , mitochondrion , chemistry , phospholipid , endoplasmic reticulum , membrane , gene
We have developed genetic and biochemical tools to examine the transport of phospholipids among organelles for the purpose of synthesizing PtdEtn within the mitochondria and Golgi. PtdSer is transported from subdomains of the ER to PtdSer decarboxylase1(Psd1p) in the mitochondria for PtdEtn synthesis, under the control of a ubiquitin ligase (Met30p), a transcription factor (Met4p), a deubiquitinating enzyme (Ubp3p), and its regulatory protein (Bre5p). Mitochondrial pools of PtdEtn can also be replenished in cells lacking Psd1p by the action of aminophospholipid transporters (Dnf1p, Dnf2p) and their regulatory subunit (Lem3p) acting at the plasma membrane to transport lyso‐PtdEtn into the cell. PtdSer transport to PtdSer decarboxylase 2 (Psd2p) in the Golgi is regulated by a PtdIns 4‐kinase (Stt4p), a lipid binding protein (PstB2p), and the C2 domains of Psd2p. The PstB2p protein binds directly to Psd2p and a protein designated Pbi1p. The Pbi1p also binds the ER tethering protein Scs2p, which associates with Stt4p. The C2 domain of Psd2p is required for the recognition of PtdSer, PtdIns and PtdIns‐4P on the donor membrane. PstB2p and Pbi1p regulate intermembrane associations by binding to phosphatidic acid and polyphosphoinositides. These findings support a mechanism for interorganelle phospholipid transport involving protein‐protein and protein lipid interactions between membranes. NIH 2R37 GM32453