期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1853, 期 4, 页码 802-809出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2014.12.017
关键词
TCR; Nanoclustering; Membrane; Lipid; Cholesterol
资金
- Excellence Initiative of the German Research Foundation [GSC-4, EXC294]
- BIOSS Center for Biological Signalling Studies
- German Research Foundation [SCH 976/2-1]
- European Union (Systems Biology of T-Cell Activation) [FP7/2007-2013 SYBILLA]
In the last decade an increasing number of plasma membrane (PM) proteins have been shown to be non-randomly distributed but instead forming submicron-sized oligomers called nanoclusters. Nanoclusters exist independently of the ligand-bound state of the receptors and their existence implies a high degree of lateral organisation of the PM and its proteins. The mechanisms that drive receptor nanodustering are largely unknown. One well-defined example of a transmembrane receptor that forms nanoclusters is the T cell antigen receptor (TCR), a multisubunit protein complex whose nanoclustering influences its activity. Membrane lipids, namely cholesterol and sphingomyelin, have been shown to contribute to TCR nanoclustering. However, the identity of the membrane microdomain in which the TCR resides remains controversial. Using a GFP-labeled TCR we show here that the resting TCR localized in the disordered domain of giant PM vesicles (GPMVs) and PM spheres (PMSs) and that single and nanoclustered TCRs are found in the high-density fractions in sucrose gradients. Both findings are indicative of non-raft localization. We discuss possible mechanisms of TCR nanoclustering in T cells. This article is part of a Special Issue entitled: Nanoscale 'membrane organisation and signalling. (C) 2014 Elsevier B.V. All rights reserved.
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