Distribution of the LDL receptor within clathrin-coated pits and caveolae in rat and human liver |
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| Authors: | Soumya Ivaturi Catherine J. Wooten Maikhanh D. Nguyen Gene C. Ness Dayami Lopez |
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| Affiliation: | 1. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), College of Arts and Sciences, North Carolina Central University, Durham, NC 27707, USA;2. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA |
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| Abstract: | Several findings suggest that the low-density lipoprotein (LDL) receptor may internalize different lipoprotein particles via diverse pathways. Using a combination of discontinuous sucrose gradients and Triton solubilization studies, we demonstrated that the LDL receptor could be located simultaneously in clathrin-coated pits and caveolae in rat and human liver and in human hepatocyte-like C3A cells. Treatment with the cholesterol biosynthesis inhibitor, zaragozic acid A, shifted the distribution of the LDL receptor to clathrin containing fractions, whereas treatment with cholesterol or LDL shifted the receptor distribution towards caveolin-1 containing fractions. The LDL-dependent shift of the LDL receptor to caveolae coincided with a reduction in internalization of Bodipy-LDL. Redistribution within plasma membrane microdomains in response to specific treatments resulting in changes in LDL receptor function represents a novel paradigm that could be exploited in the development of a new class of therapeutic drugs. |
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| Keywords: | LDL, low density lipoprotein VLDL, very low density lipoprotein LDLRAP1, LDL receptor adaptor protein-1 CH, cholesterol ZA, zaragozic acid A HC, heavy chain TS, Triton soluble TI, Triton insoluble |
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