Document Type |
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Article In Journal |
Document Title |
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KIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae KIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae |
Document Language |
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English |
Abstract |
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Multifunctional low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) recognizes and internalizes a large number of diverse ligands, including LDL and factor VIII. However, little is known about the regulation of LRP1 endocytosis. Here, we show that a microtubule-based motor protein, KIF13B, in an unexpected and unconventional function, enhances caveolin-dependent endocytosis of LRP1. KIF13B was highly expressed in the liver and was localized on the sinusoidal plasma membrane of hepatocytes. KIF13B knockout (KO) mice showed elevated levels of serum cholesterol and factor VIII, and KO MEFs showed decreased uptake of LDL. Exogenous KIF13B, initially localized on the plasma membrane with caveolae, was translocated to the vesicles in the cytoplasm with LRP1 and caveolin-1. KIF13B bound to hDLG1 and utrophin, which, in turn, bound to LRP1 and caveolae, respectively. These linkages were required for the KIF13B-enhanced endocytosis of LRP1. Thus, we propose that KIF13B, working as a scaffold, recruits LRP1 to caveolae via LRP1-hDLG1-KIF13B-utrophin-caveolae linkage and enhances the endocytosis of LRP1. |
ISSN |
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0021-9525 |
Journal Name |
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The Journal of cell biology |
Volume |
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204 |
Issue Number |
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3 |
Publishing Year |
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1435 AH
2014 AD |
Article Type |
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Article |
Added Date |
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Tuesday, March 8, 2016 |
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Researchers
Yoshimitsu Kanai | Kanai, Yoshimitsu | Investigator | | |
Daliang Wang | Wang, Daliang | Researcher | | |
Nobutaka Hirokawa | Hirokawa, Nobutaka | Researcher | | |
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