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Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface.

Authors: Chu, BB  Ge, L  Xie, C  Zhao, Y  Miao, HH  Wang, J  Li, BL  Song, BL 
Citation: Chu BB, etal., J Biol Chem. 2009 Aug 14;284(33):22481-90. doi: 10.1074/jbc.M109.034355. Epub 2009 Jun 19.
Pubmed: (View Article at PubMed) PMID:19542231
DOI: Full-text: DOI:10.1074/jbc.M109.034355

Niemann-Pick C1-like 1 (NPC1L1) plays a critical role in the enterohepatic absorption of free cholesterol. Cellular cholesterol depletion induces the transport of NPC1L1 from the endocytic recycling compartment to the plasma membrane (PM), and cholesterol replenishment causes the internalization of NPC1L1 together with cholesterol via clathrin-mediated endocytosis. Although NPC1L1 has been characterized, the other proteins involved in cholesterol absorption and the endocytic recycling of NPC1L1 are largely unknown. Most of the vesicular trafficking events are dependent on the cytoskeleton and motor proteins. Here, we investigated the roles of the microfilament and microfilament-associated triple complex composed of myosin Vb, Rab11a, and Rab11-FIP2 in the transport of NPC1L1 from the endocytic recycling compartment to the PM. Interfering with the dynamics of the microfilament by pharmacological treatment delayed the transport of NPC1L1 to the cell surface. Meanwhile, inactivation of any component of the myosin Vb.Rab11a.Rab11-FIP2 triple complex inhibited the export of NPC1L1. Expression of the dominant-negative mutants of myosin Vb, Rab11a, or Rab11-FIP2 decreased the cellular cholesterol uptake by blocking the transport of NPC1L1 to the PM. These results suggest that the efficient transport of NPC1L1 to the PM is dependent on the microfilament-associated myosin Vb.Rab11a.Rab11-FIP2 triple complex.

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RGD Object Information
RGD ID: 11533638
Created: 2016-09-08
Species: All species
Last Modified: 2016-09-08
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.