Linked Life Data

11563861

Source:http://linkedlifedata.com/resource/pubmed/id/11563861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-9-20
pubmed:abstractText
Positional cloning approaches revealed that Tangier disease (TD), a genetic high density lipoprotein deficiency, is associated with mutations in the ATP-binding cassette transporter-1 (ABCA1) gene. However, the biological function of ABCA1 is still not fully investigated. Recently, we have reported that the cells from the patients with TD had abnormal actin cytoskeletons in association with decreased expression of Cdc42, a member of RhoGTPases family. In the present study, we have found that actin cytoskeletons were altered in HEK293 cells transfected with human ABCA1 (hABCA1) cDNA. Cells expressing hABCA1 were divided into the following two groups by the distinct morphology with altered actin cytoskeletons: one had increased formation of filopodia (designated as Type I) and the other had long protrusions (designated as Type II). Type I cells had morphology similar to that of cells transfected with dominant active form of Cdc42 (Cdc42-DA, V12Cdc42Hs-DA). Type II cells had morphology similar to that of cells transfected with neural Wiskott-Aldrich Syndrome Protein (N-WASP),one of the established downstream effector molecules of Cdc42. We have obtained the data showing a possible pathway of ABCA1/Cdc42/N-WASP by the following experiments. Introduction of mutant of Cdc42 (dominant negative form of Cdc42, N17Cdc42Hs-DN) and N-WASP (N-WASP lacking verprolin homology domain, N-WASPDeltaVPH), both of which are supposed to have potential to inhibit rearrangement of actin cytoskeletons, significantly inhibited the morphological changes induced by expression of hABCA1. Immunoprecipitation study with FLAG-tagged ABCA1 (hABCA1-FLAG) revealed that Cdc42 was coimmunoprecipitated with hABCA1-FLAG. In addition, we have demonstrated possible intracellular colocalization of these two molecules in the overexpressing cells by the confocal laser microscopy. These results may suggest that hABCA1 regulates actin organization through the possible interaction with Cdc42Hs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
287
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
757-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11563861-ATP-Binding Cassette Transporters, pubmed-meshheading:11563861-Actins, pubmed-meshheading:11563861-Animals, pubmed-meshheading:11563861-Blotting, Western, pubmed-meshheading:11563861-COS Cells, pubmed-meshheading:11563861-Cell Line, pubmed-meshheading:11563861-Cell Membrane, pubmed-meshheading:11563861-Cytoskeleton, pubmed-meshheading:11563861-DNA, Complementary, pubmed-meshheading:11563861-Genes, Dominant, pubmed-meshheading:11563861-Humans, pubmed-meshheading:11563861-Microscopy, Confocal, pubmed-meshheading:11563861-Microscopy, Fluorescence, pubmed-meshheading:11563861-Nerve Tissue Proteins, pubmed-meshheading:11563861-Plasmids, pubmed-meshheading:11563861-Precipitin Tests, pubmed-meshheading:11563861-Protein Binding, pubmed-meshheading:11563861-Transfection, pubmed-meshheading:11563861-Wiskott-Aldrich Syndrome Protein, Neuronal, pubmed-meshheading:11563861-cdc42 GTP-Binding Protein
pubmed:year
2001
pubmed:articleTitle
ATP-binding cassette transporter-1 induces rearrangement of actin cytoskeletons possibly through Cdc42/N-WASP.
pubmed:affiliation
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't