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ORIGINAL RESEARCH article

Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
Volume 18 - 2024 | doi: 10.3389/fncel.2024.1505846
This article is part of the Research Topic Structure and Function of iGluR and their auxiliary subunits View all articles

Exploring the Impact of the Stargazin V143L Mutation on the Dynamics of the AMPA Receptor:Stargazin Complex

Provisionally accepted
Raquel Gouveia Raquel Gouveia 1Carlos Barreto Carlos Barreto 2Rita Melo Rita Melo 3Ana Luisa Carvalho Ana Luisa Carvalho 1Irina Sousa Moreira Irina Sousa Moreira 1*
  • 1 University of Coimbra, Science and technology Faculty, Coimbra, Portugal
  • 2 Centre for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Coimbra, Portugal
  • 3 Associação do Instituto Superior Técnico de Investigação e Desenvolvimento (IST-ID), Lisboa, Portugal

The final, formatted version of the article will be published soon.

    Stargazin, a transmembrane AMPAR regulatory protein (TARP), plays a crucial role in facilitating the transport of AMPA receptors to the cell surface, stabilising their localisation at synapses and influencing their gating properties. The primary objective of this study was to investigate the effect of the V143L mutation in stargazin, previously linked to intellectual disability, on the interaction between stargazin and AMPA receptors. To achieve this, we conducted a thorough examination of eight distinct molecular dynamics simulations of AMPA receptor-stargazin complexes, each associated with different conductance levels. Through extensive analysis of complex interface structures and dynamics, we revealed that the stargazin V143L mutation had a more pronounced destabilising effect on complexes with lower conductance levels than on the conductive states of the receptor, suggesting a potential association with impaired synaptic transmission in individuals with this mutation.

    Keywords: stargazin, AMPAR, V143L mutation, Intellectual Disability, Protein-protein interface, structure and dynamic

    Received: 03 Oct 2024; Accepted: 09 Dec 2024.

    Copyright: © 2024 Gouveia, Barreto, Melo, Carvalho and Moreira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Irina Sousa Moreira, University of Coimbra, Science and technology Faculty, Coimbra, Portugal

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