| The small GTPase Cdc42 interacts with Niemann-Pick C1 Like 1 (NPC1L1) and controls its movement from endocytic recycling compartment to plasma membrane in a cholesterol dependent manner. | |
| | |
MedLine Citation:
|
PMID: 21844200 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Niemann-Pick C1 Like 1 (NPC1L1) is a multi-transmembrane protein that mediates the absorption of dietary and biliary cholesterol through vesicular endocytosis. The subcellular localization of NPC1L1 is regulated by cholesterol. Cholesterol depletion induces the transport of NPC1L1 to plasma membrane (PM) from endocytic recycling compartment that requires MyoVb-Rab11a-Rab11FIP2 triple complex, and cholesterol-replenishment renders the internalization of NPC1L1 together with cholesterol. Here, we find that GTP-bound Cdc42 interacts with NPC1L1. Cholesterol depletion regulates the activation of Cdc42 and enhances NPC1L1-Cdc42 interaction. Over-expression of constitutive GTP-bound Cdc42 mutant form or knockdown of Cdc42 inhibits the transport of NPC1L1 to the PM and disturbs the cholesterol-regulated binding of NPC1L1 to Rab11a, MyoVb and actin. Knockdown of Cdc42 downstream effectors N-WASP or Arp3 also leads to the similar results. In liver specific Cdc42 knockout (Cdc42 LKO) mice, NPC1L1 fails to localize to bile canaliculi, and the biliary cholesterol cannot be efficiently reabsorbed. These results indicate that Cdc42 controls the cholesterol-regulated transport and localization of NPC1L1, and plays a role in cholesterol absorption. |
| | |
Authors:
|
Chang Xie; Na Li; Zheng-Jun Chen; Bo-Liang Li; Bao-Liang Song |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2011-8-15 |
Journal Detail:
|
Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
|
Created Date: 2011-8-16 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Shanghai Institute of Biochemistry and Cell Biology, China; |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: JNK dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochon...
Next Document: Single-stranded noncoding RNAs mediate local epigenetic alterations at gene promoters in rat cell li...