Phospholipid transfer protein interacts with and stabilizes ATP-binding cassette transporter A1 and enhances cholesterol efflux from cells.
Phospholipid lipid transfer protein (PLTP) is ubiquitously expressed in animal tissues and plays multiple roles in lipoprotein metabolism, but the function of peripheral PLTP is still poorly understood. Here we show that one of its possible functions is to transport cholesterol and phospholipids from cells to lipoprotein particles by a process involving PLTP interactions with cellular ATP-binding cassette transporter A1 (ABCA1). When ABCA1 was induced in murine macrophages or ABCA1-transfected baby hamster kidney cells, PLTP gained the ability to promote cholesterol and phospholipid efflux from cells. Although PLTP alone had lipid efflux activity, its maximum activity was observed in the presence of high density lipoprotein particles. Pulsechase studies showed that the interaction of PLTP with ABCA1-expressing cells played a role in promoting lipid efflux. Overexpression of ABCA1 dramatically increased binding of both PLTP and apoA-I to common sites on the cell surface. Both PLTP and apoA-I were covalently cross-linked to ABCA1, each protein blocked cross-linking of the other, and both PLTP and apoA-I stabilized ABCA1 protein. These results are consistent with PLTP and apoA-I binding to ABCA1 at the same or closely related sites. Thus, PLTP mimics apolipoproteins in removing cellular lipids by the ABCA1 pathway, except that PLTP acts more as an intermediary in the transfer of cellular lipids to lipoprotein particles.
Oram
John F
JF
Department of Medicine, University of Washington, Seattle, Washington 98195-6426, USA. joram@u.washington.edu
Wolfbauer
Gertrud
G
Vaughan
Ashley M
AM
Tang
Chongren
C
Albers
John J
JJ
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D009154:Mutation; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D018076:DNA, Complementary; D008074:Lipoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D011994:Recombinant Proteins; D002784:Cholesterol