SNAP23 regulates KCC2 membrane insertion and activity following mZnR/GPR39 activation in hippocampalneurons.

ABSTRACT: Modulation of the neuronal K⁺/Cl^- cotransporter 2 (KCC2) activity, which mediates Cl^- export, is critical to neuronal function. Here, we demonstrate that KCC2 interacts with the SNARE protein synaptosome-associated protein 23, SNAP23, an essential component of membrane insertion machinery. Using KCC2 truncated mutants, we show that KCC2 C-terminal domain is essential for membrane targeting and SNAP23-dependent upregulation of KCC2 activity triggered by activation of the Zn²⁺-sensitive receptor mZnR/GPR39 in HEK293 cells. Expression of SNAP23 phosphorylation-insensitive mutants or inhibition of its upstream activator IκB kinase (IKK) prevents mZnR/GPR39 upregulation of KCC2 activity in mouse hippocampal neurons. We further find that SNAP23 interac

SUBMITTER: Asraf H 

PROVIDER: S-EPMC8800107 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature