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/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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Adaptor Proteins, Signal Transducing*
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Animals
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COS Cells
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Carrier Proteins / analysis
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism*
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Cortactin
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Cytoskeleton / chemistry
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Cytoskeleton / ultrastructure
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Disks Large Homolog 4 Protein
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Hippocampus / cytology
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Microfilament Proteins / analysis
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Microfilament Proteins / metabolism*
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Microscopy, Immunoelectron
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Molecular Sequence Data
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Multigene Family
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Nerve Tissue Proteins / analysis
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Nerve Tissue Proteins / metabolism*
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Neurons / chemistry*
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Neurons / cytology
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Neurons / metabolism
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Protein Structure, Tertiary
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Rabbits
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Rats
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Receptors, N-Methyl-D-Aspartate / analysis
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Receptors, N-Methyl-D-Aspartate / metabolism*
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SAP90-PSD95 Associated Proteins
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Sequence Homology, Amino Acid
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Synapses / chemistry
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Synapses / metabolism
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Synapses / ultrastructure
Substances
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Actins
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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Cortactin
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Cttn protein, rat
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Microfilament Proteins
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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SAP90-PSD95 Associated Proteins
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Shank1 protein, rat
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Shank3 protein, rat
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postsynaptic density proteins
Associated data
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GENBANK/AF131951
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GENBANK/AF133301