Document Detail

Nanoscale organization of multiple GPI-anchored proteins in living cell membranes.
MedLine Citation:
PMID:  14980224     Owner:  NLM     Status:  MEDLINE    
Cholesterol and sphingolipid-enriched "rafts" have long been proposed as platforms for the sorting of specific membrane components including glycosyl-phosphatidylinositol-anchored proteins (GPI-APs), however, their existence and physical properties have been controversial. Here, we investigate the size of lipid-dependent organization of GPI-APs in live cells, using homo and hetero-FRET-based experiments, combined with theoretical modeling. These studies reveal an unexpected organization wherein cell surface GPI-APs are present as monomers and a smaller fraction (20%-40%) as nanoscale (<5 nm) cholesterol-sensitive clusters. These clusters are composed of at most four molecules and accommodate diverse GPI-AP species; crosslinking GPI-APs segregates them from preexisting GPI-AP clusters and prevents endocytosis of the crosslinked species via a GPI-AP-selective pinocytic pathway. In conjunction with an analysis of the statistical distribution of the clusters, these observations suggest a mechanism for functional lipid-dependent clustering of GPI-APs.
Pranav Sharma; Rajat Varma; R C Sarasij; Ira; Karine Gousset; G Krishnamoorthy; Madan Rao; Satyajit Mayor
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  116     ISSN:  0092-8674     ISO Abbreviation:  Cell     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-24     Completed Date:  2004-04-15     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  577-89     Citation Subset:  IM    
National Centre for Biological Science (TIFR), UAS-GKVK Campus, GKVK PO, Bangalore 560 065, India.
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MeSH Terms
CHO Cells
Cell Membrane / metabolism*,  physiology*,  ultrastructure*
Cells, Cultured
Cholesterol / metabolism
Cross-Linking Reagents / pharmacology
Fluorescence Resonance Energy Transfer
Green Fluorescent Proteins
Image Processing, Computer-Assisted
Lipid Metabolism
Lipids / chemistry
Luminescent Proteins / metabolism
Membrane Microdomains / chemistry
Models, Biological
Time Factors
Reg. No./Substance:
0/Cross-Linking Reagents; 0/Lipids; 0/Luminescent Proteins; 147336-22-9/Green Fluorescent Proteins; 57-88-5/Cholesterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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