Experience alters hippocampal and cortical network communication via a KIBRA-dependent mechanism

Modulation of GABAAreceptor trafficking by WWC2 reveals class-specific mechanisms of synapse regulation by WWC family proteins

“…Analysis of single cell RNAseq data from mouse hippocampus and cortex 32 reveals that, similar to KIBRA 22 , WWC2 is expressed in the majority of excitatory cortical and hippocampal neuron cell types (85% of identified excitatory cell types, Fig. 1B) but only a subset of inhibitory neurons (38% of inhibitory cell types, Fig.…”

“…Deletion of KIBRA causes aberrant trafficking and expression of AMPAR subunits GluA1 and GluA2 in the hippocampus and impairs synaptic plasticity and memory 18,19,21 . Additionally, loss of KIBRA impairs experience-induced changes in hippocampal and cortical circuit dynamics that support memory consolidation 22…”

“…Additionally, loss of KIBRA impairs experience-induced changes in hippocampal and cortical circuit dynamics that support memory consolidation 22 WWC2 shares approximately 50% residue identity with KIBRA (human WWC2 vs. KIBRA: 49.37%, mouse WWC2 vs. KIBRA: 48.87%) and contains protein-protein and 3 protein-lipid interacting domains common to the WWC family: two N-terminal WW domains, a C2 domain, an atypical protein kinase C (aPKC) binding site, and a C-terminal PDZ ligand 23,24 (Fig. 1A).…”