On multivalent receptor activity of GM1 in cholesterol containing membranes

0436776 - ÚFCH JH 2016 RIV US eng J - Journal Article
Šachl, Radek - Amaro, Mariana - Aydogan, Gokcan - Koukalová, Alena - Mikhaylov, I. I. - Boldyrev, I. A. - Humpolíčková, Jana - Hof, Martin
On multivalent receptor activity of GM1 in cholesterol containing membranes.
Biochimica Et Biophysica Acta-Molecular Cell Research. Roč. 1853, č. 4 (2015), s. 850-857. ISSN 0167-4889. E-ISSN 1879-2596
R&D Projects: GA ČR(CZ) GC14-03141J; GA MŠMT LH13259
Institutional support: RVO:61388955
Keywords : Gangliosides * Cholera toxin * Fluorescence correlation spectroscopy
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 5.128, year: 2015

Gangliosides located at the outer leaflet of plasma membrane aremolecules that either participate in recognizing of exogenous ligandmolecules or exhibit their own receptor activity,which are both essential phenomena for cell communication and signaling aswell as for virus and toxin entry. Regulatorymechanisms of lipid-mediated recognition are primarily subjected to the physical status of the membrane in close vicinity of the receptor. Concerning the multivalent receptor activity of the ganglioside GM1, several regulatory strategies dealing with GM1 clustering and cholesterol involvement have been proposed. So far however, merely the isolated issues were addressed and no interplay between them investigated. In this work, several advanced fluorescence techniques such as Z-scan fluorescence correlation spectroscopy, Förster resonance energy transfer combined with Monte Carlo simulations, and a newly developed fluorescence antibunching assay were employed to give a more complex portrait of clustering and cholesterol involvement in multivalent ligand recognition of GM1. Our results indicate that membrane properties have an impact on a fraction of GM1 molecules that is not available for the ligand binding. While at low GM1 densities (~1 %) it is the cholesterol that turns GM1 headgroups invisible, at higher GM1 level (~4 %) it is purely the local density of GM1molecules that inhibits the recognition. At mediumGM1 content, cooperation of the two phenomena occurs. This article is part of a Special Issue entitled: Nanoscale membrane orgainisation and signalling.
Permanent Link: http://hdl.handle.net/11104/0240473