期刊
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
卷 1798, 期 6, 页码 1081-1089出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2010.02.021
关键词
Tumor necrosis factor (TNF); Plasma membrane receptor; Receptor complex; Fluorescence correlation spectroscopy; TNF receptor associated factor (TRAF); Microdomains
资金
- Deutsche Forschungsgemeinschaft [SFB 495, A4, A6]
- European Commission
- Center for Systems Biology Stuttgart
The proinflammatory cytokine tumor necrosis factor (TNF) binds two distinct plasma membrane receptors. TNFR1 and TNFR2. We have produced different receptor mutants fused with enhanced green fluorescent protein to study their membrane dynamics by fluorescence correlation spectroscopy (FCS). TNFR1 mutants show diffusion constants of approximately 1.2 x 10(-9) cm(2)/s and a broad distribution of diffusion times, which is hardly affected by ligand binding. However, cholesterol depletion enhances their diffusion, suggesting a constitutive affinity to cholesterol rich membrane microdomains. In contrast, TNFR2 and mutants thereof diffuse rather fast ((D) over bar =3.1 x 10(-9) cm(2)/s) with a marked reduction after 30 min of TNF treatment ((D) over bar= 0.9 x 10(-9) cm(2)/s). This reduction cannot be explained by the formation of higher ordered receptor clusters, since the fluorescence intensity of TNF treated receptors indicate the presence of a few receptor molecules per complex only. Together, these data point to a topological segregation of the two TNF receptors in different microcompartments of the plasma membrane independent of the cytoplasmic signaling domains of the receptors. (C) 2010 Elsevier B.V. All rights reserved.
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