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Fundacion Ramon Areces, Grant/Award Number: CIVP20A6612; 'la Caixa' Foundation, Grant/Award Number: LCF/PR/HR22/52420019; NextGenerationEU/PRTR; MCIN/AEI/10.13039/501100011033, Grant/Award Number: CEX2020-001041-S, EQC2021-007053-P, PLEC2022-009235 and PLEC2022-009298; Comunidad de Madrid, Grant/Award Number: S2022/B M D - 7 3 3 3 - C M ( I N M U N O VA R- C M ) ; MCIN/AEI/10.13039/501100011033, Grant/Award Number: PID2020- 119399RB-I00 and PID2021- 122348NB-I00; European Regional Development Fund (ERDF) A way of making Europe

Analysis of institutional authors

Lopez-Corcuera, BCorresponding Author

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August 4, 2024
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Role of palmitoylation on the neuronal glycine transporter GlyT2

Publicated to:JOURNAL OF NEUROCHEMISTRY. 168 (9): 2056-2072 - 2024-07-20 168(9), DOI: 10.1111/jnc.16181

Authors: Felipe, R; Felipe, R; Sarmiento-Jimenez, J; Sarmiento-Jimenez, J; Camafeita, E; Camafeita, E; Vazquez, J; Vazquez, J; Lopez-Corcuera, B; Lopez-Corcuera, B

Affiliations

CIBER Enfermedades CardioVasc CIBERCV, Madrid, Spain - Author
Ctr Nacl Invest Cardiovasc ISCIII, Madrid, Spain - Author
IdiPAZ Hosp Univ La Paz, Madrid, Spain - Author
Univ Autonoma Madrid, Dept Biol Mol, Inst Biol Mol IUBM, Ctr Biol Mol Severo Ochoa,CSIC, Madrid, Spain - Author

Abstract

The neuronal glycine transporter GlyT2 removes glycine from the synaptic cleft through active Na+, Cl-, and glycine cotransport contributing to the termination of the glycinergic signal as well as supplying substrate to the presynaptic terminal for the maintenance of the neurotransmitter content in synaptic vesicles. Patients with mutations in the human GlyT2 gene (SLC6A5), develop hyperekplexia or startle disease (OMIM 149400), characterized by hypertonia and exaggerated startle responses to trivial stimuli that may have lethal consequences in the neonates as a result of apnea episodes. Post-translational modifications in cysteine residues of GlyT2 are an aspect of structural interest we analyzed. Our study is compatible with a reversible and short-lived S-acylation in spinal cord membranes, detectable by biochemical and proteomics methods (acyl-Rac binding and IP-ABE) confirmed with positive and negative controls (palmitoylated and non-palmitoylated proteins). According to a short-lived modification, direct labeling using click chemistry was faint but mostly consistent. We have analyzed the physiological properties of a GlyT2 mutant lacking the cysteines with high prediction of palmitoylation and the mutant is less prone to be included in lipid rafts, an effect also observed upon treatment with the palmitoylation inhibitor 2-bromopalmitate. This work demonstrates there are determinants of lipid raft inclusion associated with the GlyT2 mutated cysteines, which are presumably modified by palmitoylation.

Keywords

AnimalsAssociationCalciuCysteineExpressionGlycineGlycine plasma membrane transport proteinsGlyt2HumansIdentificationLipid raftsLipoylationLocalizationMechanismsMembrane microdomainsMembrane raftsMutationNeuronsPalmitoylationPhenotypeProtein processing, post-translationalRatsS-palmitoylationSlc6a5 protein, humanSlc6a5 protein, ratSpinal cordTraffickingTransporteTransporter

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF NEUROCHEMISTRY due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry.

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-07-19:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 1.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 2 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.25.

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (Felipe, R) and Last Author (LOPEZ CORCUERA, BEATRIZ).

the author responsible for correspondence tasks has been LOPEZ CORCUERA, BEATRIZ.