title: The role of signalling in cellular cholesterol homeostasis.
abstract: Cholesterol is a vital lipid and performs diverse functions on a whole body and cellular level. However, excess cellular cholesterol is toxic, and thus, elegant mechanisms have evolved to tightly regulate this important lipid. The regulation of cholesterol homeostasis is an area of intense research, and the role that signalling plays is gradually becoming more widely recognised. Cholesterol homeostasis is achieved through intricate mechanisms involving synthesis, uptake, and efflux. Although there is a large body of work elucidating these cholesterol-related pathways, less is known about the role of signalling in these processes. Here, we discuss the variety of ways that signalling impacts on these modes and levels of cholesterol homeostasis, including transcriptional regulation. Most work thus far has investigated the role of kinases in cholesterol efflux (especially on ATP-binding cassette transporter A1, ABCA1), and therefore constitutes a major focus of this review. We also indicate further avenues to explore in the area of signalling in cellular cholesterol homeostasis.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, NSW, Australia.
authors.forename: Winnie
authors.initials: W
authors.lastname: Luu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sharpe
authors.forename: Ingrid C
authors.initials: IC
authors.lastname: Gelissen
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000502:physiology; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D000071518:Liver X Receptors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000502:physiology
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011973:Receptors, LDL; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D000242:Cyclic AMP; D006903:Hydroxymethylglutaryl CoA Reductases; D053614:Janus Kinase 2; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin
keywords: ABCA1; cholesterol; efflux; kinase; phosphorylation; signalling