What is the function of ABCA1 transporter?
Physiological role ABCA1 mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins (apoA1 and apoE) (reverse cholesterol transport), which then form nascent high-density lipoproteins (HDL). It also mediates the transport of lipids between Golgi and cell membrane.
Is ABCA1 a lipid transfer protein?
ABCA1 functions as a lipid transporter because it mediates the transfer of cellular phospholipid (PL) and free (unesterified) cholesterol (FC) to apoA-I and related proteins present in the extracellular medium. The presence of active ABCA1 in the PM promotes binding of apoA-I to the cell surface.
What is the ABCA1 gene?
The ABCA1 gene belongs to a group of genes called the ATP-binding cassette family, which provides instructions for making proteins that transport molecules across cell membranes. The ABCA1 protein is produced in many tissues, with high amounts found in the liver and in immune system cells called macrophages.
What is ABCA1 gene?
What is cholesterol efflux?
Cholesterol efflux. Cholesterol efflux, a part of RCT, is a pathway transferring intracellular cholesterol from macrophages or other cells to extracellular acceptors such as apolipoprotein A-I (apoA-I) of high-density lipoprotein (HDL).
What are the types of ABC transporters?
Around the same time, biochemical studies on the mammalian multi-drug resistance (MDR) export pump P-glycoprotein revealed the presence of the very same motifs in its ATP-binding domain, demonstrating that the family of ABC transporters was represented not only in bacteria but also higher eukaryotes, including mammals.
Where are ABC transporters?
The ABC transporters comprise a large and multifunctional family of structurally related membrane proteins that are located in the plasma membrane of the cells or in the membrane of various cellular organelles.
What are the functions of triglycerides?
Triglycerides provide your body with energy, but their main function is to store energy for later use. The food you eat contains calories in the form of carbohydrates, protein and fat. When you consume more calories than your body can use, it stores those calories in the form of triglycerides.
Why is cholesterol transported as lipoproteins?
Because lipids, such as cholesterol and triglycerides, are insoluble in water these lipids must be transported in association with proteins (lipoproteins) in the circulation.
How many ABC transporter are there?
There are 48 ABC transporters in humans [8,9] and many of these have been shown to be responsible for or involved in disease states, including cystic fibrosis, Tangier disease, adrenoleukodystrophy, and cancer (see below).
How do microbes use ABC transporter?
ATP-binding cassette (ABC) transporters couple ATP hydrolysis to the uptake and efflux of solutes across the cell membrane in bacteria and eukaryotic cells. In bacteria, these transporters are important virulence factors because they play roles in nutrient uptake and in secretion of toxins and antimicrobial agents.
How is the expression of ABCA1 related to cholesterol?
Notably, ABCA1 expression is regulated through key signaling pathways mediated by excess cholesterol (Fig. 1 ), which will be described briefly below. ABCA1 cell signaling pathways. The cholesterol-dependent signaling pathways which regulate ABCA1 include the LXR/RXR and SREBP-2 pathway.
What are the signaling pathways associated with ABCA1?
The cholesterol-independent signaling pathways associated with ABCA1 regulation include the NF-κB, TLR4/Myleoid88, JAK2/STAT3, cAMP/PKA, apoptosis pathways involved in regulating inflammatory responses Cholesterol in cells can be converted into oxysterols, which in turn can potently upregulate ABCA1 expression [ 4 ].
What is the role of ABCA1 in the RCT?
ABCA1 transporter plays an important role in maintaining cellular cholesterol homeostasis by participating in the reverse cholesterol transport pathway (RCT) [ 5 ]. ABCA1 expressed in peripheral cells facilitates the export of cellular cholesterol to its extracellular acceptor protein apolipoprotein-A1 (apoA-1) [ 6 ].
What happens to Abca1 when it is repressed?
Furthermore, it is known that when ABCA1 is repressed, excess cholesterol builds up in alveolar cells, damaging surfactant function and increasing the inflammatory response which has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), asthma and other lung diseases (reviewed in [ 1, 17, 20 ]).