Journal
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
Volume 1798, Issue 6, Pages 1081-1089Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamem.2010.02.021
Keywords
Tumor necrosis factor (TNF); Plasma membrane receptor; Receptor complex; Fluorescence correlation spectroscopy; TNF receptor associated factor (TRAF); Microdomains
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB 495, A4, A6]
- European Commission
- Center for Systems Biology Stuttgart
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available