Sharpin, a novel postsynaptic density protein that directly interacts withthe Shank family of proteins

The Shank family of proteins (also termed CortBP, ProSAP, or Synamon) is hi ghly enriched in the postsynaptic density (PSD) of excitatory synapses in b rain. Shank contains multiple domains for protein-protein interactions, inc luding ankyrin repeats, SH3 domain, PDZ domain, SAM domain, and an extensiv e proline-rich region. We have identified a novel protein, termed Sharpin, that directly interacts with the ankyrin repeats of Shank, Sharpin is enric hed in the PSD and forms a complex with Shank in heterologous cells and bra in. Immunostaining reveals the presence of Sharpin at excitatory synapses a nd its colocalization with Shank. While the C-terminal half of Sharpin inte racts with Shank, the N-terminal half of Sharpin mediates homomultimerizati on. Considering the fact that the ankyrin repeats and the SH3 domain of Sha nk can be truncated by alternative splicing, these results define Sharpin a s a novel PSD protein that may regulate the complexity of the Shank-based p rotein network in an alternative splicing-dependent manner.