title: Lysophosphatidylcholine Acyltransferase 1 (LPCAT1) Specifically Interacts with Phospholipid Transfer Protein StarD10 to Facilitate Surfactant Phospholipid Trafficking in Alveolar Type II Cells.
abstract: Pulmonary surfactant, a mixture of proteins and phospholipids, plays an important role in facilitating gas exchange by maintaining alveolar stability. Saturated phosphatidylcholine (SatPC), the major component of surfactant, is synthesized both de novo and by the remodeling of unsaturated phosphatidylcholine (PC) by lyso-PC acyltransferase 1 (LPCAT1). After synthesis in the endoplasmic reticulum, SatPC is routed to lamellar bodies (LBs) for storage prior to secretion. The mechanism by which SatPC is transported to LB is not understood. The specificity of LPCAT1 for lyso-PC as an acyl acceptor suggests that formation of SatPC via LPCAT1 reacylation is a final step in SatPC synthesis prior to transport. We hypothesized that LPCAT1 forms a transient complex with SatPC and specific phospholipid transport protein(s) to initiate trafficking of SatPC from the endoplasmic reticulum to the LB. Herein we have assessed the ability of different StarD proteins to interact with LPCAT1. We found that LPCAT1 interacts with StarD10, that this interaction is direct, and that amino acids 79-271 of LPCAT1 and the steroidogenic acute regulatory protein-related lipid transfer (START) domain of START domain-containing protein 10 (StarD10) are sufficient for this interaction. The role of StarD10 in trafficking of phospholipid to LB was confirmed by the observation that knockdown of StarD10 significantly reduced transport of phospholipid to LB. LPCAT1 also interacted with one isoform of StarD7 but showed no interaction with StarD2/PC transfer protein.
authors.affiliation: From the Divisions of Pulmonary Biology and.
authors.forename: Sui
authors.initials: S
authors.lastname: Lin
authors.affiliation: From the Divisions of Pulmonary Biology and.
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
authors.affiliation: Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Changsuk
authors.initials: C
authors.lastname: Moon
authors.affiliation: Pulmonary Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229.
authors.forename: Anjaparavanda P
authors.initials: AP
authors.lastname: Naren
authors.affiliation: From the Divisions of Pulmonary Biology and john.shannon@cchmc.org.
authors.forename: John M
authors.initials: JM
authors.lastname: Shannon
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D051379:Mice; D010713:Phosphatidylcholines / Q000096:biosynthesis / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis* / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D060066:Protein Interaction Maps / Q000235:genetics; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D010713:Phosphatidylcholines; D010743:Phospholipids; D010750:Phosphoproteins; D011663:Pulmonary Surfactants; C000600335:STARD7 protein, mouse; C488091:Stard10 protein, mouse; D008243:1-Acylglycerophosphocholine O-Acyltransferase; C526203:Lpcat1 protein, mouse
keywords: lipid trafficking; lipid-binding protein; phospholipid; protein expression; protein-protein interaction