and Pcdha proteins interact, and may form multimeric complexes with Pcdhb proteins (Han et al., 2010; Murata et al., 2004; Schalm et al., 2010). Moreover, both Pcdha and Pcdhg proteins are tyrosine phosphorylated in mature neurons, suggesting that they mediate intracellular signaling (Schalm et al., 2010). Co-immunoprecipitation experiments using a pan-Pcdhg antibody in brain lysate indicated that the A- and B-type Pcdhg isoforms in Pcdhgtcko/tcko mutants still form complexes with Pcdha proteins, they are tyrosine phosphorylated and they interact with Src, suggesting that they are capable of mediating intracellular signaling in the absence of the C-type isoforms (Figures 4D–E). We conclude that Pcdhgtcko/tcko is not a severe hypomorphic or dominant negative mutant, and that expression and function of the remaining A- and B-type Pcdhg isoforms is not appreciably distinct from those of wild type mice.
