Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library.

ABSTRACT:

Introduction

The neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission. KCC2 also plays a pivotal role in the development of excitatory glutamatergic neurotransmission by promoting dendritic spine maturation. The cytoplasmic C-terminal domain (KCC2-CTD) plays a critical regulatory role in the molecular mechanisms controlling the cotransporter activity through dimerization, phosphorylation, and protein interaction.

Methods

To identify novel CTD regulatory motifs, we used the Mu transposon-based mutagenesis system to generate a library of KCC2 mutants with 5 amino acid insertions randomly distributed within the KCC2-CTD. We determined the insertion positions in 288 mutants by

SUBMITTER: Uvarov P 

PROVIDER: S-EPMC11774852 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature