Mechanisms of Intracellular Cholesterol Transport

来源 :第11届海峡两岸细胞生物学学术研讨会 | 被引量 : 0次 | 上传用户:JK0803_zhangke
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Cholesterol is dynamically transported among organelles, which is essential for multiple cellular functions.Intracellular cholesterol transport contains many aspects including how cholesterol in plasma membrane moves to endocytic recycling compartments and how low-density lipoprotein (LDL)-derived cholesterol leaves lysosome.For the first question, we demonstrate that Niemann-Pick C1 Like 1 (NPC1L1) mediates intestinal cholesterol absorption through vesicular endocytosis.We identified an endocytic signal, YVNxxF (where x stands for any amino acid) , in the cytoplasmic C-terminal tail of NPC1L1.Cholesterol binding on the N-terminal domain (NTD) of NPC1L1 released the YVNxxF from association with plasma membrane (PM) and enabled Numb binding.Numb, a clathrin adaptor specifically recognized this motif and recruited clathrin for internalization.Disrupting the NPC 1 L1-Numb interaction decreased cholesterol uptake.Ablation of Numb in mouse intestine significantly reduced dietary cholesterol absorption and plasma cholesterol level.
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