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

Neuron | Jul 13, 1999

http://www.ncbi.nlm.nih.gov/pubmed/10433268

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/PSD-95 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.

Pubmed ID: 10433268 RIS Download

Mesh terms: Actins | Adaptor Proteins, Signal Transducing | Animals | COS Cells | Carrier Proteins | Cortactin | Cytoskeleton | Hippocampus | Intracellular Signaling Peptides and Proteins | Membrane Proteins | Microfilament Proteins | Microscopy, Immunoelectron | Molecular Sequence Data | Multigene Family | Nerve Tissue Proteins | Neurons | Protein Structure, Tertiary | Rabbits | Rats | Receptors, N-Methyl-D-Aspartate | Sequence Homology, Amino Acid | Synapses

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Associated grants

  • Agency: NIDA NIH HHS, Id: DA103009
  • Agency: NINDS NIH HHS, Id: NS29879
  • Agency: NINDS NIH HHS, Id: NS35050

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