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• W3139133060 abstract "Abstract Mutations in PRoline Rich Transmembrane protein 2 (PRRT2) cause pleiotropic syndromes including benign infantile epilepsy, paroxysmal kinesigenic dyskinesia, episodic ataxia, that share the paroxysmal character of the clinical manifestations. PRRT2 is a neuronal protein that plays multiple roles in the regulation of neuronal development, excitability, and neurotransmitter release. To better understand the physiopathology of these clinical phenotypes, we investigated PRRT2 interactome in mouse brain by a pulldown-based proteomic approach and identified α1 and α3 Na + /K + ATPase (NKA) pumps as major PRRT2-binding proteins. We confirmed PRRT2 and NKA interaction by biochemical approaches and showed their colocalization at neuronal plasma membrane. The acute or constitutive inactivation of PRRT2 had a functional impact on NKA. While PRRT2-deficiency did not modify NKA expression and surface exposure, it caused an increased clustering of α3-NKA on the plasma membrane. Electrophysiological recordings showed that PRRT2-deficiency in primary neurons impaired NKA function during neuronal stimulation without affecting pump activity under resting conditions. Both phenotypes were fully normalized by re-expression of PRRT2 in PRRT2-deficient neurons. In addition, the NKA-dependent afterhyperpolarization that follows high-frequency firing was also reduced in PRRT2-silenced neurons. Taken together, these results demonstrate that PRRT2 is a physiological modulator of NKA function and suggest that an impaired NKA activity contributes to the hyperexcitability phenotype caused by PRRT2 deficiency." @default.
• W3139133060 created "2021-03-29" @default.
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• W3139133060 date "2021-03-17" @default.
• W3139133060 modified "2023-10-18" @default.
• W3139133060 title "An interaction between PRRT2 and Na+/K+ ATPase contributes to the control of neuronal excitability" @default.
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• W3139133060 doi "https://doi.org/10.1038/s41419-021-03569-z" @default.
• W3139133060 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7969623" @default.
• W3139133060 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33731672" @default.
• W3139133060 hasPublicationYear "2021" @default.
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