RGD Reference Report - The ATP-binding cassette transporter-2 (ABCA2) regulates esterification of plasma membrane cholesterol by modulation of sphingolipid metabolism. - Rat Genome Database

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The ATP-binding cassette transporter-2 (ABCA2) regulates esterification of plasma membrane cholesterol by modulation of sphingolipid metabolism.

Authors: Davis, Warren 
Citation: Davis W, Biochim Biophys Acta. 2014 Jan;1841(1):168-79. doi: 10.1016/j.bbalip.2013.10.019. Epub 2013 Nov 5.
RGD ID: 14697729
Pubmed: PMID:24201375   (View Abstract at PubMed)
PMCID: PMC4437569   (View Article at PubMed Central)
DOI: DOI:10.1016/j.bbalip.2013.10.019   (Journal Full-text)

The ATP-binding cassette transporters are a large family (~48 genes divided into seven families A-G) of proteins that utilize the energy of ATP-hydrolysis to pump substrates across lipid bilayers against a concentration gradient. The ABC "A" subfamily is comprised of 13 members and transport sterols, phospholipids and bile acids. ABCA2 is the most abundant ABC transporter in human and rodent brain with highest expression in oligodendrocytes, although it is also expressed in neurons. Several groups have studied a possible connection between ABCA2 and Alzheimer's disease as well as early atherosclerosis. ABCA2 expression levels have been associated with changes in cholesterol and sphingolipid metabolism. In this paper, we hypothesized that ABCA2 expression level may regulate esterification of plasma membrane-derived cholesterol by modulation of sphingolipid metabolism. ABCA2 overexpression in N2a neuroblastoma cells was associated with an altered bilayer distribution of the sphingolipid ceramide that inhibited acylCoA:cholesterol acyltransferase (ACAT) activity and cholesterol esterification. In contrast, depletion of endogenous ABCA2 in the rat schwannoma cell line D6P2T increased esterification of plasma membrane cholesterol following treatment with exogenous bacterial sphingomyelinase. These findings suggest that control of ABCA2 expression level may be a key locus of regulation for esterification of plasma membrane-derived cholesterol through modulation of sphingolipid metabolism.




Biological Process

  
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Original Reference(s)
Abca2Ratnegative regulation of phospholipid biosynthetic process involved_inIMP PMID:24201375ARUK-UCL 
Abca2Ratnegative regulation of sphingolipid biosynthetic process involved_inIMP PMID:24201375ARUK-UCL 
Abca2Ratnegative regulation of steroid metabolic process acts_upstream_ofIMP PMID:24201375ARUK-UCL 


Genes (Rattus norvegicus)
Abca2  (ATP binding cassette subfamily A member 2)