DISP3, a sterol-sensing domain-containing protein that links thyroid hormone action and cholesterol metabolism

0334067 - ÚMG 2010 RIV US eng J - Journal Article
Zíková, Martina - Corlett, Alicia - Bendová, Zdeňka - Pajer, Petr - Bartůněk, Petr
DISP3, a sterol-sensing domain-containing protein that links thyroid hormone action and cholesterol metabolism.
Molecular Endocrinology. Roč. 23, č. 4 (2009), s. 520-528. ISSN 0888-8809
R&D Projects: GA AV ČR IAA500520705
Grant - others:EC(XE) LSHM-CT-2005-018652
Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50110509
Keywords : thyroid hormone receptor * cholesterol metabolism * sterol-sensing domain
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 5.257, year: 2009

In the body the brain is the most cholesterol-rich organ. Despite this, remarkably little is known about the mechanisms in the brain that regulate cholesterol homeostasis. Thyroid hormone receptors, activated in response to thyroid hormone (T3), are known to modulate the level of serum cholesterol via complex regulatory pathways. By screening for T3-regulated genes we identified Disp3, a sterol-sensing protein that is related to the Dispatched family of proteins. Using the model of hyperthyroidism in vivo we observed modulation of the Disp3 expression. DISP3 localizes within the endoplasmic reticulum and was further found to co-localize with cholesterol. Ectopic expression of DISP3 resulted in elevated cholesterol levels combined with an altered cholesterol distribution. Taken together, we propose that DISP3 represents a new molecular link between thyroid hormone and cholesterol metabolism in the brain.
Permanent Link: http://hdl.handle.net/11104/0178901