Andersen-Tawil Syndrome Is Associated With Impaired PIP₂ Regulation of the Potassium Channel Kir2.1.

ABSTRACT: Andersen-Tawil syndrome (ATS) type-1 is associated with loss-of-function mutations in KCNJ2 gene. KCNJ2 encodes the tetrameric inward-rectifier potassium channel Kir2.1, important to the resting phase of the cardiac action potential. Kir-channels' activity requires interaction with the agonist phosphatidylinositol-4,5-bisphosphate (PIP₂). Two mutations were identified in ATS patients, V77E in the cytosolic N-terminal "slide helix" and M307V in the C-terminal cytoplasmic gate structure "G-loop." Current recordings in Kir2.1-expressing HEK cells showed that each of the two mutations caused Kir2.1 loss-of-function. Biotinylation and immunostaining showed that protein expression and trafficking of Kir2.1 to the plasma membrane were not affected by the mutations. To tes

SUBMITTER: Handklo-Jamal R 

PROVIDER: S-EPMC7243181 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature