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

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Abstract

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.

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Acknowledgements

This work was supported by funding Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, to R.C. Santos, H.F. Loponte), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, to D.M.S. Lucena, A.R. Todeschini), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ, to A.R. Todeschini).

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Author notes

  1. Ronan C. M. Santos, Daniela MS Lucena, and Hector F. B. R. Loponte contributed equally to the work.

Authors and Affiliations

  1. Carlos Chagas Filho Biophysics’ Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Ronan C. M. Santos, Daniela M. S. Lucena, Hector F. B. R. Loponte, Wagner B. Dias & Adriane R. Todeschini

  2. Paulo de Goes Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902, Brazil

    Frederico Alisson-Silva

  3. Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Pernambuco, 50740-465, Brazil

    Roberto D. Lins

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  1. Ronan C. M. Santos
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Correspondence to Adriane R. Todeschini.

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Santos, R.C.M., Lucena, D.M.S., Loponte, H.F.B.R. et al. GM2/GM3 controls the organizational status of CD82/Met microdomains: further studies in GM2/GM3 complexation. Glycoconj J 39, 653–661 (2022). https://doi.org/10.1007/s10719-022-10061-z

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