Bei-Bei Chu

Publications (3)15.1 Total impact

• Source

  Available from: Chang Xie

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

  Bei-Bei Chu, Liang Ge, Chang Xie, Yang Zhao, Hong-Hua Miao, Jing Wang, Bo-Liang Li, Bao-Liang Song
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  ABSTRACT: 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.
  Journal of Biological Chemistry 07/2009; 284(33):22481-90. · 4.77 Impact Factor
• Article: Requirement of myosin Vb/Rab11a/Rab11-FIP2 complex in cholesterol-regulated translocation of Niemann-Pick C1 like 1 protein to the cell surface

  Bei-Bei Chu, Liang Ge, Chang Xie, Yang Zhao, Hong-Hua Miao, Jing Wang, Bo-Liang Li, Bao-Liang Song
  [show abstract] [hide abstract]
  ABSTRACT: 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 endocytic recycling compartment (ERC) to 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 microfilament and microfilament-associated triple complex composed of myosin Vb, Rab11a and Rab11-FIP2 in the transport of NPC1L1 from ERC to PM. Interference of the dynamics of 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 PM. These results suggest that the efficient transport of NPC1L1 to PM is dependent on the microfilament-associated myosin Vb/Rab11a/Rab11-FIP2 triple complex.
  Journal of Biological Chemistry 06/2009; · 4.77 Impact Factor
• Article: Membrane topology of human NPC1L1, a key protein in enterohepatic cholesterol absorption.

  Jiang Wang, Bei-Bei Chu, Liang Ge, Bo-Liang Li, Yan Yan, Bao-Liang Song
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  ABSTRACT: The Niemann-Pick C1 Like 1 (NPC1L1) is a predicted polytopic membrane protein that is critical for cholesterol absorption. NPC1L1 takes up free cholesterol into cells through vesicular endocytosis. Ezetimibe, a clinically used cholesterol absorption inhibitor, blocks the endocytosis of NPC1L1 thereby inhibiting cholesterol uptake. Human NPC1L1 is a 1,332-amino acid protein with a putative sterol-sensing domain (SSD) that shows sequence homo-logy to HMG-CoA reductase (HMGCR), Niemann-Pick C1 (NPC1), and SREBP cleavage-activating protein (SCAP). Here, we use protease protection and immunofluorescence in selectively permeabilized cells to study the topology of human NPC1L1. Our data indicate that NPC1L1 contains 13 transmembrane helices. The NH2-terminus of NPC1L1 is in the lumen while the COOH-terminus projects to the cytosol. human NPC1L1 contains seven small cytoplasmic loops--four small and three large luminal loops--one of which has been reported to bind ezetimibe. Ezetimibe-glucuronide, the major metabolite of ezetimibe in vivo, can block the internalization of NPC1L1 and cholesterol. The membrane topology of NPC1L1 is similar to that of NPC1, and the putative SSD of NPC1L1 is oriented in the same manner as those of HMGCR, NPC1, and SCAP. The defined topology of NPC1L1 provides necessary information for further dissecting the functions of the different domains of NPC1L1.
  The Journal of Lipid Research 04/2009; 50(8):1653-62. · 5.56 Impact Factor