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Title: Nanoscale Organization of Multiple GPI-Anchored Proteins in Living Cell Membranes
Authors: Sharma, Pranav
Varma, Rajat
Sarasij, R.C.
Karine Gousset, Ira
Krishnamoorthy, G.
Rao, Madan
Mayor, Satyajit
Issue Date: Feb-2004
Publisher: Elsevier B.V.
Citation: Cell, 2004, Vol.116, p577-589
Abstract: 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.
Description: Restricted Access.
ISSN: 0092-8674
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Copyright: 2004 Elsevier B.V.
Appears in Collections:Research Papers (TP)

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