검색 상세

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

초록/요약

The Shank family of proteins(also termed cortBP, ProSAP, or Synamon) are highly enriched in the postsynaptic density(PSD) of excitatory synapses in brain. Shank contains multiple domains for protein-protein interactions including ankyrin repeats, SH3 domain, PDZ domain, SAM domain and an extensive proline-rich region. Proteins that bind to Shank have been identified: the PDZ domain binds to the GKAP/SAPAP family of proteins, the proline-rich region interacts with Homer/Vesl and cortactin, and the SAM domain mediates homomultimerization of Shank. The functions of the N-terminal ankyrin repeats and the SH3 domain of Shank are unknown. We have identified a novel protein, termed Sharpin, that directly interacts with the N-terminal region of Shank containing the ankyrin repeats. Sharpin is widely expressed at mRNA and protein levels in many tissues and enriched in the PSD in brain. Sharpin forms a complex with Shank in heterologous cells and can be coimmunoprecipitated with Shank, GKAP and PSD-95 from brain extracts. Immunostaining reveals the presence of Sharpin at excitatory synapses and its partial colocalization with Shank. While the C-terminal half of Sharpin interacts with Shank, the N-terminal half of Sharpin mediates homomultimerization. These results define a new component of the postsynaptic PSD-95/GKAP/Shank complex at excitatory synapses.

more