2026-07-21T07:57:53Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/258652025-12-18T13:00:45Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Felipe, R
author
Sarmiento-Jiménez, J
author
Camafeita, E
author
Vázquez, J
author
López-Corcuera, B
funder
Unión Europea. Comisión Europea. NextGenerationEU
funder
Fundación Ramón Areces
funder
Fundación La Caixa
funder
Comunidad de Madrid (España)
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
2024-12-09T11:09:56Z
2024-12-09T11:09:56Z
2024-09
J Neurochem. 2024 Sep;168(9):2056-2072.
Journal of Neurochemistry
39032066
https://hdl.handle.net/20.500.12105/25865
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.
eng
GlyT2
cysteine
glycine
lipid rafts
palmitoylation
transporter
Role of palmitoylation on the neuronal glycine transporter GlyT2.
research article
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URL
https://repisalud.isciii.es/bitstreams/f57abf2e-7c33-4b37-b429-0f8110864e3e/download
File
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a7cf6d964a6f235f036592b5b08d2d17
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Role of palmitoylation_J Neurochem_2024.pdf