2.A.30.1.14
KCl symporter KCC2. It influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines (Gauvain et al., 2011). It plays a role in inhibitory and excitatory neurotransmission in neurons (Chamma et al., 2012). KCC2 transport activity requires the highly conserved L(675) in the C-terminal β1 strand (Döding et al., 2012). Direct physical coupling between the GABA-A receptor and the KCC2 chloride transporter underlies ionic plasticity in cerebellar purkinje neurons in response to brain-derived neurotrophic factor (BDNF) (Huang et al., 2013).  KCC2 is neuron-specific and is essential for Cl(-) homeostasis and fast inhibitory synaptic transmission in the mature CNS. KCC2 is regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter (Ivakine et al. 2013). Loss of the Neto2:KCC2 interaction reduced KCC2-mediated Cl^- extrusion, resulting in decreased synaptic inhibition in hippocampal neurons.  KCC2 mediates the efflux of Cl^-out of neurons and plays a role in inhibitory GABAergic and glycinergic neurotransmission. It also participates in the regulation of various physiological processes of neurons, including cell migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis (Wu et al. 2016). Down-regulation of KCC2 is associated with multiple neurological diseases and is particularly relevant to acute central nervous system (CNS) injury. Structural changes in the extracellular loop 2 of the murine KCC2 potassium chloride cotransporter modulate ion transport (Hartmann et al. 2021). Gephyrin, the main scaffolding molecule at GABAergic synapses, interacts with KCC2 to regulate its surface expression and function in cortical neurons (Al Awabdh et al. 2021). The expression system influences the stability, maturation efficiency, and oligomeric properties of  KCC2 (Kok et al. 2024). VEGF, but not BDNF, prevents the downregulation of KCC2 induced by axotomy in extraocular motoneurons (Capilla-López et al. 2024).