A spotlight on the StAR protein

Commonly shortened to StAR, the steroidogenic acute regulatory protein plays a key role in mitochondrial transport within steroid-producing cells, regulating hormone production by controlling cholesterol transfer within the mitochondria. StAR is a member of the START domain protein family, and is also known as START domain-containing protein 1, or STARD1. Antibody suppliers may list it under either or both names. Star antibodies have proven important in several areas of research.

StAR is a protein of 285 amino acids, located on chromosome 8p. It is found in a number of steroid-producing areas including the ovary, testes and adrenal cortex. Its primary purpose is to mediate transfer of cholesterol from the outer mitochondrial membrane to the inner surface, so that the enzyme cytochrome P450scc can cleave the side chain, performing the first stage of steroid synthesis.

Cholesterol is a lipophilic protein and is therefore unable to cross the aqueous membrane layer unaided. Antibody studies have shown StAR to be the most important mediator of this process, assisted by a number of other proteins. These include TSPO, SCP2 and the Steroidogenic Activator Polypeptide SAP.

It is known that the signalling sequence by which StAR is targeted to the mitochondria is a two-stage process, with activity increased by phosphorylation at position 195. Cholesterol transfer is achieved via the START (StAR-related transfer) domain. However, the exact mechanism of action by which StAR achieves cholesterol transport remains unclear. A number of mechanisms have been suggested, including binding to cholesterol in a shuttle-type process; however, the evidence points to it acting more like a channel. Other hypotheses include desorption of the cholesterol through the membrane; the creation of contact sites, or interaction with PBR.

StAR expression may not be as restricted as we think. Recently, J.M Taylor and others published a study showing StAR expression in macrophages, where it stimulated production of 27-hydroxycholesterol, suggesting a possible anti-inflammatory role in cardiovascular disease. An earlier study suggested a role in bile production. Although neither of these studies has proven conclusive, it seems the StAR antibodies we at Novus Biologicals have on our antibody database have more secrets yet to unveil.

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