Mechanistically, reduced GluR2 palmitoylation associates with decreased expression and palmitoylation of the palmitoyl acyltransferase DHHC3, while levels of depalmitoylating enzymes remain unchanged. In vitro, DHHC3 enhances GluR2 palmitoylation, supporting a direct enzymatic relationship. Partial restoration of frataxin expression rescues GluR2 and DHHC3 protein levels and partially restores GluR2 palmitoylation. These findings identify impaired GluR2 palmitoylation as an early, selective synaptic alteration in FRDA and implicate dysregulated lipid-dependent post-translational modification as a mechanism linking frataxin deficiency to cerebellar synaptic vulnerability.
Tuesday, August 11, 2026
Impaired Glur2 palmitoylation in cerebellar Purkinje cells of a Friedreich ataxia mouse model
Elizabeth Mercado-Ayón, Jennifer Coulman, Jia-Ying Lee, Eunjoo Lancaster, Elliot Goga, Mohammad Asad, Eric Witze, David R. Lynch,
Impaired Glur2 palmitoylation in cerebellar Purkinje cells of a Friedreich ataxia mouse model,
Experimental Neurology,
2026,
115955,
ISSN 0014-4886,
doi:10.1016/j.expneurol.2026.115955.
