Understanding Sitosterolemia: How ABCG5-ABCG8 Dimer Affects Blood Sterol Levels

Thu, 08/22/2013 - 09:15

The ATP binding cassette (ABC) transporter family is the largest and most diverse family of membrane transport proteins and, as the name suggests, uses the energy generated by ATP hydrolysis to transport substrates across membranes. Eukaryotic ABC transporters are divided in to full or half transporters, and in to seven sub-families named A through to G (1). ABCG is a half-transporter in that it contains one ABC domain and one transmembrane domain; full-transporters contain two of each domain type, whilst half-transporters such as ABCG function by forming homo- or hetero-dimers to configure a membrane-spanning channel that facilitates substrate transport.

Western Blot: ABCG8 Antibody Western Blot: ABCG8 Antibody

There are five human ABCG genes (ABCG1, ABCG2, ABCG4, ABCG5 and ABCG8), all of which are implicated in the transport of lipids. The genes for ABCG5 and ABCG8 are located adjacent to each other on chromosome 2p21, and their expression levels are highest in liver and intestine (2). The proteins encoded by these genes form a heterodimer known as sterolin; both were identified in the search for genetic causes of a rare autosomal-recessive lipid metabolism disorder known as sitosterolemia. Individuals with this condition experience premature atherosclerosis and early onset cardiovascular disease due to the accumulation of dietary plant sterols such as sitosterol (3). In healthy individuals, ABCG8-ABCG5 heterodimers mediate the secretion of these sterols from enterocytes back in to the intestinal lumen, and from hepatocytes in to bile, for excretion from the body. Individuals with sitosterolemia show significantly elevated plasma sterol concentrations due to dysfunction of this transport system (4). Patients with sitosterolemia are currently treated by diet modulation to reduce plant sterol intake to the lowest levels possible, however in the majority of cases serum levels of plant sterols do not reach the normal range (5).

ABCG8 antibodies can be used to assess the cellular localization of ABCG8 protein; for example Klett, et. al. have demonstrated by immunohistochemistry and by Western blotting that ABCG8 is found at bile duct epithelia and at the brush border of the small intestine (6).

  1. PMID: 19416657
  2. PMID: 11099417
  3. PMID: 21554546
  4. PMID: 15599566
  5. PMID: 20543520
  6. PMID: 15383151

Novus Biologicals offers various ABCG8 reagents for your research needs including:

Written by Emma Easthope

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