ATP-binding cassette transporter A1
(ABCA1) is a cAMP
-dependent and sulfonylurea-sensitive anion transporter belonging to the ATP-binding cassette family. ABCA1 is involved in the regulation of apolipoprotein AI
(apoAI)-mediated cholesterol efflux and high-density lipoproteins
(HDL) metabolism (1). In the brain, ABCA1 transports cholesterol to apoE
, the major CNS apolipoprotein, where it influences motor function and synaptic morphology.
ABCA1 is comprised of 2,261 amino acids with a theoretical molecular weight of 254 kDa and human ABCA1 shares 97% amino acid identity with mouse ABCA1. The general structure of ABCA consists of two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs). ABCA1 is a widely distributed cell-membrane protein with the highest expression found in macrophages. DHHC8
mediated palmitoylation of ABCA1 is essential for its localization to the plasma membrane
and expression of mouse ABCA1 (not human) is induced by cAMP analogs (2). ABCA1 is phosphorylated at Ser1042 and Ser2054 by PKA, with Ser2054 being key for regulating phospholipid efflux. Mutations in ABCA1 have been linked to atherosclerosis and the progression of metabolic syndrome phenotypes: high density lipoprotein deficiency type 1 (HDLD1); also known as Tangier disease (TGD), and high density lipoprotein deficiency type 2 (HDLD2); also known as familial hypoalphalipoproteinemia (FHA) (3).
1.Oram JF, Lawn RM. (2001) ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J Lipid Res. 42(8):1173-9. PMID: 11483617
2.Singaraja RR, Kang MH, Vaid K, Sanders SS, Vilas GL, Arstikaitis P, Coutinho J, Drisdel RC, El-Husseini Ael D, Green WN, Berthiaume L, Hayden MR. (2009) Palmitoylation of ATP-binding cassette transporter A1 is essential for its trafficking and function. Circ Res. 105(2):138-47. PMID: 19556522
3.Attie AD. (2007) ABCA1: at the nexus of cholesterol, HDL and atherosclerosis. Trends in Biochemical Sciences 32(4):172-9. PMID: 17324574