Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin.
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.
Naisbitt
S
S
Howard Hughes Medical Institute, Department of Neurobiology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Kim
E
E
Tu
J C
JC
Xiao
B
B
Sala
C
C
Valtschanoff
J
J
Weinberg
R J
RJ
Worley
P F
PF
Sheng
M
M
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D051356:Cortactin; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins / Q000032:analysis / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011817:Rabbits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000032:analysis / Q000378:metabolism*; D000074407:SAP90-PSD95 Associated Proteins; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051356:Cortactin; C495870:Cttn protein, rat; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000074407:SAP90-PSD95 Associated Proteins; C120531:Shank1 protein, rat; C120532:Shank3 protein, rat; C033652:postsynaptic density proteins