Campus Units

Chemistry, Ames Laboratory

Document Type

Article

Publication Version

Accepted Manuscript

Publication Date

1-2018

Journal or Book Title

European Biophysics Journal

Volume

47

Issue

1

First Page

39

Last Page

48

DOI

10.1007/s00249-017-1227-5

Abstract

Membrane diffusion is one of the key mechanisms in the cellular function of receptors. The signaling of receptors for advanced glycation end-products (RAGE) has been extensively studied in the context of several pathological conditions, however, very little is known about RAGE diffusion. To fill this gap, RAGE lateral diffusion is probed in native, cholesterol-depleted, and cytoskeleton-altered cellular conditions. In native GM07373 cellular conditions, RAGE has a 90% mobile fraction and an average diffusion coefficient of 0.3 μm2/s. When depolymerization of the actin cytoskeleton is inhibited with the small molecule jasplakinolide (Jsp), the RAGE mobile fraction and diffusion coefficient decrease by 22 and 37%, respectively. In contrast, depolymerizing the filamentous actin cytoskeleton using the small molecule cytochalasin D (CD) does not alter the RAGE diffusion properties. There is a 70 and 50% decrease in phosphorylation of extracellular signal-regulated kinase (p-ERK) when the actin cytoskeleton is disrupted by CD or Jsp, respectively, in RAGE-expressing GM07373 cells. Disrupting the actin cytoskeleton in GM07373 cells that do not express detectable amounts of RAGE results in no change in p-ERK. Cholesterol depletion results in no statistically significant change in the diffusion properties of RAGE or p-ERK. This work presents a strong link between the actin cytoskeleton and RAGE diffusion and downstream signaling, and serves to further our understanding of the factors influencing RAGE lateral diffusion.

Comments

This is a post-peer-review, pre-copyedit version of an article published in European Biophysics Journal. The final authenticated version is available online at: http://dx.doi.org/10.1007/s00249-017-1227-5. Posted with permission.

Copyright Owner

Springer Nature

Language

en

File Format

application/pdf

Published Version

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