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PMID:10433268

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Citation

Naisbitt, S, Kim, E, Tu, JC, Xiao, B, Sala, C, Valtschanoff, J, Weinberg, RJ, Worley, PF and Sheng, M (1999) Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23:569-82

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.

Links

PubMed

Keywords

Actins/metabolism; Adaptor Proteins, Signal Transducing; Animals; COS Cells; Carrier Proteins/analysis; Carrier Proteins/chemistry; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cortactin; Cytoskeleton/chemistry; Cytoskeleton/ultrastructure; Hippocampus/cytology; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Microfilament Proteins/analysis; Microfilament Proteins/metabolism; Microscopy, Immunoelectron; Molecular Sequence Data; Multigene Family; Nerve Tissue Proteins/analysis; Nerve Tissue Proteins/metabolism; Neurons/chemistry; Neurons/cytology; Neurons/metabolism; Protein Structure, Tertiary; Rabbits; Rats; Receptors, N-Methyl-D-Aspartate/analysis; Receptors, N-Methyl-D-Aspartate/metabolism; Sequence Homology, Amino Acid; Synapses/chemistry; Synapses/metabolism; Synapses/ultrastructure

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:KCNA4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P78352

F

Seeded From UniProt

complete

RAT:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97836

F

Seeded From UniProt

complete

RAT:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WV48

F

Seeded From UniProt

complete

HUMAN:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P15385

F

Seeded From UniProt

complete

HUMAN:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97836-5

F

Seeded From UniProt

complete

RAT:DLGP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31016

F

Seeded From UniProt

complete

RAT:DLGP1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WV48

F

Seeded From UniProt

complete

HUMAN:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P78352

F

Seeded From UniProt

complete

HUMAN:DLG4

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9WV48

F

Seeded From UniProt

complete

RAT:SHAN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P31016

F

Seeded From UniProt

complete

RAT:SHAN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97836

F

Seeded From UniProt

complete

RAT:SHAN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P97836-5

F

Seeded From UniProt

complete

RAT:SHAN3

enables

GO:0042802: identical protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9JLU4

F

Seeded From UniProt

complete

See also

References

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