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.
URI:	http://hdl.handle.net/2289/2727
ISSN:	0092-8674
Alternative Location:	http://dx.doi.org/10.1016/S0092-8674(04)00167-9
Copyright:	2004 Elsevier B.V.
Appears in Collections:	Research Papers (TP)

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