Stimulation of Slack K+ Channels Alters Mass at the Plasma Membrane by Triggering Dissociation of a Phosphatase-Regulatory Complex
Citations Over TimeTop 21% of 2016 papers
Abstract
Human mutations in the cytoplasmic C-terminal domain of Slack sodium-activated potassium (KNa) channels result in childhood epilepsy with severe intellectual disability. Slack currents can be increased by pharmacological activators or by phosphorylation of a Slack C-terminal residue by protein kinase C. Using an optical biosensor assay, we find that Slack channel stimulation in neurons or transfected cells produces loss of mass near the plasma membrane. Slack mutants associated with intellectual disability fail to trigger any change in mass. The loss of mass results from the dissociation of the protein phosphatase 1 (PP1) targeting protein, Phactr-1, from the channel. Phactr1 dissociation is specific to wild-type Slack channels and is not observed when related potassium channels are stimulated. Our findings suggest that Slack channels are coupled to cytoplasmic signaling pathways and that dysregulation of this coupling may trigger the aberrant intellectual development associated with specific childhood epilepsies.
Related Papers
- → Studies on ion‐exchange membranes. XXXII. Heterogeneity in ion‐exchange membranes(1970)47 cited
- → Charge mosaic membranes prepared from laminated structures of PVA-based charged layers1. Preparation and transport properties of charged mosaic membranes(2007)34 cited
- → Synthetic an biological membranes(1982)6 cited
- → 516—Synthetic and biological membranes(1982)
- 나노 구조물을 이용한 농도 차 발전 시스템에 관한 연구(2012)