Theodore L Steck
Research Summary / Selected Publications
My long-term research interest is in membrane biochemistry. Over the years, I have studied the molecular organization of the human red cell membrane and the membrane biology of the ameba, Dictyostelium discoideum. In addition, the disposition of cell cholesterol has been a recurrent focus. We are currently investigating cellular cholesterol homeostasis: how cells sense their need for this essential plasma membrane lipid and make appropriate adjustments to keep it in balance. We suggest that cells gauge the magnitude of the bulk pool of cholesterol in the plasma membrane by sensing the high activity of the cholesterol in excess of phospholipid partners. This active excess sets the size of the sterol pool in the endoplasmic reticulum and mitochondria through the flow of cholesterol between the cell surface and intracellular membranes. The endoplasmic reticulum and mitochondrial pools then set the level of activity of several regulatory elements in those membranes that then mediate sterol homeostasis. The elements of this cholesterol sensing system and how it can be manipulated are under investigation.
My long-term research interest is in membrane biochemistry. Over the years, I have studied the molecular organization of the human red cell membrane and the membrane biology of the ameba, Dictyostelium discoideum. In addition, the disposition of cell cholesterol has been a recurrent focus. We are currently investigating cellular cholesterol homeostasis: how cells sense their need for this essential plasma membrane lipid and make appropriate adjustments to keep it in balance. We suggest that cells gauge the magnitude of the bulk pool of cholesterol in the plasma membrane by sensing the high activity of the cholesterol in excess of phospholipid partners. This active excess sets the size of the sterol pool in the endoplasmic reticulum and mitochondria through the flow of cholesterol between the cell surface and intracellular membranes. The endoplasmic reticulum and mitochondrial pools then set the level of activity of several regulatory elements in those membranes that then mediate sterol homeostasis. The elements of this cholesterol sensing system and how it can be manipulated are under investigation.
Lange, Y., Ye, J., and Steck, T.L. (2012). Activation mobilizes the cholesterol in the late endosomes-lysosomes of niemann pick type C cells. PLoS One 7, e30051.
Steck, T.L., and Lange, Y. (2010). Cell cholesterol homeostasis: Mediation by active cholesterol. Trends in Cell Biology 20, 680-687.
Lange, Y., Ye, J., Duban, M.-E., and Steck, T. L. (2009) Activation of Membrane Cholesterol by 63 Amphipaths, Biochemistry 48, 8505-8515.
Lange, Y., Steck, T. L., Ye, J., Lanier, M. H., Molugu, V., and Ory, D. (2009) Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol, Journal of Lipid Research 50, 1881-1888.
Lange, Y., and Steck, T. L. (2008) Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol, Prog Lipid Res 47, 319-332.
Lange Y., Ory D.S., Ye, J., Lanier, M.H., Hsu, F.F., and Steck, T.L. (2008) Effectors of rapid homeostatic responses of endoplasmic reticulum cholesterol and 3-hydroxy-3-methylglutaryl-CoA reductase. J. Biol. Chem. 283:1445-1455.
Lange, Y., Ye, J., and Steck, T.L. (2007) Scrambling of phospholipids activates red cell membrane cholesterol. Biochemistry, 46:2233-2238.
Ratajczak M.K., Ko, Y.T., Lange, Y., Steck. T.L., Lee, K.Y. (2007) Cholesterol displacement membrane phospholipids by hexadecanol. Biophys J. 93:2038-2047.
Lange, Y., J. Ye, and T.L. Steck (2005) Activation of membrane cholesterol by displacement from phospholipids. J Biol Chem. 280:36126-31.
Lange Y, Ye J, Steck TL. (2004). How cholesterol homeostasis is regulated by plasma membrane cholesterol in excess of phospholipids. Proc Natl Acad Sci USA. 101,1664-11667.
Steck, T.L., Ye, J., and Lange, Y. (2002). Probing red cell membrane cholesterol movement with cyclodextrin. Biophys. J., 83, 2118-2125.
Lange, Y., Ye, J., and Steck, T.L. (2012). Activation mobilizes the cholesterol in the late endosomes-lysosomes of niemann pick type C cells. PLoS One 7, e30051.
Steck, T.L., and Lange, Y. (2010). Cell cholesterol homeostasis: Mediation by active cholesterol. Trends in Cell Biology 20, 680-687.
Lange, Y., Ye, J., Duban, M.-E., and Steck, T. L. (2009) Activation of Membrane Cholesterol by 63 Amphipaths, Biochemistry 48, 8505-8515.
Lange, Y., Steck, T. L., Ye, J., Lanier, M. H., Molugu, V., and Ory, D. (2009) Regulation of fibroblast mitochondrial 27-hydroxycholesterol production by active plasma membrane cholesterol, Journal of Lipid Research 50, 1881-1888.
Lange, Y., and Steck, T. L. (2008) Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol, Prog Lipid Res 47, 319-332.
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