Encephalopathy-causing mutations in Gβ₁ (GNB1) alter regulation of neuronal GIRK channels.

ABSTRACT: Mutations in the GNB1 gene, encoding the Gβ₁ subunit of heterotrimeric G proteins, cause GNB1 Encephalopathy. Patients experience seizures, pointing to abnormal activity of ion channels or neurotransmitter receptors. We studied three Gβ₁ mutations (K78R, I80N and I80T) using computational and functional approaches. In heterologous expression models, these mutations did not alter the coupling between G protein-coupled receptors to G_i/o, or the Gβγ regulation of the neuronal voltage-gated Ca²⁺ channel Ca_V2.2. However, the mutations profoundly affected the Gβγ regulation of the G protein-gated inwardly rectifying potassium channels (GIRK, or Kir3). Changes were observed in Gβ₁ protein expression levels, Gβγ bindin

SUBMITTER: Reddy HP 

PROVIDER: S-EPMC8426278 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature