Journal Article

GM2/GM3 controls the organizational status of CD82/Met microdomains: further studies in GM2/GM3 complexation

Lucena, Daniela M. S, Todeschini, Adriane R, Lins, Roberto D, Santos, Ronan C. M, Loponte, Hector F. B. R, Alisson-Silva, Frederico, Dias, Wagner B

2022

Overview

At cell surface gangliosides might associate with signal transducers proteins, grown factor receptors, integrins, small G-proteins and tetraspanins establishing microdomains, which play important role in cell adhesion, cell activation, motility, and growth. Previously, we reported that GM2 and GM3 form a heterodimer that interacts with the tetraspanin CD82, controlling epithelial cell mobility by inhibiting integrin-hepatocyte growth factor-induced cMet tyrosine kinase signaling. By using molecular dynamics simulations to study the molecular basis of GM2/GM3 interaction we demonstrate, here, that intracellular levels of Ca2+ mediate GM2/GM3 complexation via electrostatic interaction with their carboxyl groups, while hydrogen bonds between the ceramide groups likely aid stabilizing the complex. The presence of GM2/GM3 complex alters localization of CD82 on cell surface and therefore downstream signalization. These data contribute for the knowledge of how glycosylation may control signal transduction and phenotypic changes.

• Publisher: Springer Nature B.V
• Subject: Antigens / c-Met protein / Calcium (intracellular) / Cell activation / Cell adhesion / Cell adhesion & migration / Cell surface / Ceramide / Electrostatic properties / Epithelial cells / Gangliosides / Glycosylation / Hepatocyte growth factor / Hydrogen bonding / Integrins / Intracellular levels / Kinases / Localization / Microscopy / Molecular dynamics / Motility / Protein-tyrosine kinase / Proteins / Signal transduction / Simulation