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PMID:19542231

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Citation

Chu, BB, Ge, L, Xie, C, Zhao, Y, Miao, HH, Wang, J, Li, BL and Song, BL (2009) Requirement of myosin Vb.Rab11a.Rab11-FIP2 complex in cholesterol-regulated translocation of NPC1L1 to the cell surface. J. Biol. Chem. 284:22481-90

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.

Links

PubMed PMC2755969 Online version:10.1074/jbc.M109.034355

Keywords

Actin Cytoskeleton/chemistry; Animals; Carrier Proteins/chemistry; Cell Line, Tumor; Cell Membrane/metabolism; Cholesterol/chemistry; Cholesterol/metabolism; Endocytosis; Genes, Dominant; Membrane Proteins/chemistry; Membrane Transport Proteins/chemistry; Models, Biological; Myosins/chemistry; Protein Transport; RNA, Small Interfering/metabolism; Rats; rab GTP-Binding Proteins/chemistry

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:D3ZD48

involved_in

GO:1903078: positive regulation of protein localization to plasma membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RB11A

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UHC9

F

Seeded From UniProt

complete

RAT:RB11A

involved_in

GO:1903078: positive regulation of protein localization to plasma membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:MYO5B

involved_in

GO:1903078: positive regulation of protein localization to plasma membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:RFIP2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UHC9

F

Seeded From UniProt

complete

HUMAN:NPCL1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q7L804

F

Seeded From UniProt

complete

HUMAN:NPCL1

enables

GO:0031267: small GTPase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P62491

F

Seeded From UniProt

complete

HUMAN:NPCL1

enables

GO:0031489: myosin V binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9ULV0

F

Seeded From UniProt

complete

HUMAN:MYO5B

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UHC9

F

Seeded From UniProt

complete

HUMAN:RB11A

involved_in

GO:0016192: vesicle-mediated transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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