Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin

Scott Naisbitt, Kim Eunjoon, Jian Cheng Tu, Bo Xiao, Carlo Sala, Juli Valtschanoff, Richard J. Weinberg, Paul F. Worley, Morgan Sheng

Research output: Contribution to journalArticlepeer-review

721 Scopus citations

Abstract

NMDA receptors are linked to intracellular cytoskeletal and signaling molecules via the PSD-95 protein complex. We report a novel family of postsynaptic density (PSD) proteins, termed Shank, that binds via its PDZ domain to the C terminus of PSD-95-associated protein GKAP. A ternary complex of Shank/GKAP/PSD95 assembles in heterologous cells and can be coimmunoprecipitated from rat brain. Synaptic localization of Shank in neurons is inhibited by a GKAP splice variant that lacks the Shank-binding C terminus. In addition to its PDZ domain, Shank contains a proline-rich region that binds to cortactin and a SAM domain that mediates multimerization. Shank may function as a scaffold protein in the PSD, potentially cross-linking NMDA receptor/PSD-95 complexes and coupling them to regulators of the actin cytoskeleton.

Original languageEnglish (US)
Pages (from-to)569-582
Number of pages14
JournalNeuron
Volume23
Issue number3
DOIs
StatePublished - Jul 1999

ASJC Scopus subject areas

  • General Neuroscience

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