KIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae

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KIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae

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....

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KIF13B erects an endocytic scaffold

M icrotubule-based kinesin motor proteins have many cellular functions, including the transport of various cargoes to different parts of the cell (1). Kanai et al. uncover an unexpected , motor-independent function for one kinesin, KIF13B, in promoting the endocy-tosis of a membrane receptor that regulates cholesterol levels in the blood (2). There are 45 kinesins in the human genome, and the f...

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LRP1 mediates Hedgehog-induced endocytosis of the GPC3-Hedgehog complex.

Glypican-3 (GPC3) is a heparan sulfate (HS) proteoglycan that is bound to the cell membrane through a glycosylphosphatidylinositol link. This glypican regulates embryonic growth by inhibiting the hedgehog (Hh) signaling pathway. GPC3 binds Hh and competes with Patched (Ptc), the Hh receptor, for Hh binding. The interaction of Hh with GPC3 triggers the endocytosis and degradation of the GPC3-Hh ...

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Macrophage LRP1 contributes to the clearance of von Willebrand factor.

The relationship between low-density lipoprotein receptor-related protein-1 (LRP1) and von Willebrand factor (VWF) has remained elusive for years. Indeed, despite a reported absence of interaction between both proteins, liver-specific deletion of LRP1 results in increased VWF levels. To investigate this discrepancy, we used mice with a macrophage-specific deficiency of LRP1 (macLRP1(-)) because...

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Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis.

OBJECTIVE The purpose of this study was to determine the significance of the intracellular NPxYxxL motif of LRP1 for the atheroprotective role of this multifunctional receptor. METHODS AND RESULTS LRP1 knock-in mice carrying an inactivating mutation in the NPxYxxL motif were crossed with LDLR-deficient mice, a model for atherosclerosis. In this LDLR(-/-) background the mutated mice showed a m...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2014

ISSN: 1540-8140,0021-9525

DOI: 10.1083/jcb.201309066