Phosphoregulation of the intracellular termini of K⁺-Cl^- cotransporter 2 (KCC2) enables flexible control of its activity.

ABSTRACT: The pivotal role of K⁺-Cl^- cotransporter 2 (KCC2) in inhibitory neurotransmission and severe human diseases fosters interest in understanding posttranslational regulatory mechanisms such as (de)phosphorylation. Here, the regulatory role of the five bona fide phosphosites Ser³¹, Thr³⁴, Ser⁹³², Thr⁹⁹⁹, and Thr¹⁰⁰⁸ was investigated by the use of alanine and aspartate mutants. Tl⁺-based flux analyses in HEK-293 cells demonstrated increased transport activity for S932D (mimicking phosphorylation) and T1008A (mimicking dephosphorylation), albeit to a different extent. Increased activity was due to changes in intrinsic activity, as it was not caused by increased cell-surface abundance. Substitutions of

SUBMITTER: Cordshagen A 

PROVIDER: S-EPMC6222103 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature