DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95.
BACKGROUND
The human homologue of the Drosophila discs large tumour suppressor protein (hDLG) and closely related proteins such as postsynaptic density protein 95 kDa (PSD-95) are associated with N-methyl-D-aspartate receptors (NMDA-R) and Shaker-type K+ channels, and are thought to be involved in their clustering.


RESULTS
We have identified a protein named DAP-1 that binds to the guanylate kinase-like domains of hDLG and PSD-95. DAP-1 was found to associate with hDLG, PSD-95, NMDA-R and adenomatous polyposis coli protein (APC). Furthermore, we found that DAP-1 is specifically expressed in the brain and colocalizes with PSD-95 and APC in mouse cerebellum. We also found that DAP-1 is colocalized with PSD-95 and NMDA-R at the synapses in cultured rat hippocampal neurons.


CONCLUSIONS
Our findings suggest that DAP-1 may play several roles in the molecular organization of synapses and neuronal cell signalling by interacting with hDLG and PSD-95, which in turn are associated with receptors, ion channels and APC.
Satoh
K
K
Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Japan.
Yanai
H
H
Senda
T
T
Kohu
K
K
Nakamura
T
T
Okumura
N
N
Matsumine
A
A
Kobayashi
S
S
Toyoshima
K
K
Akiyama
T
T
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000276:immunology / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D016253:Microscopy, Immunoelectron / Q000379:methods; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D011233:Precipitin Tests; D011506:Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D000074407:SAP90-PSD95 Associated Proteins; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D051017:Apoptosis Regulatory Proteins; D003598:Cytoskeletal Proteins; C091572:DAP protein, human; C513314:DLG1 protein, human; C000614187:DLGAP1 protein, human; D000074288:Discs Large Homolog 1 Protein; D000076122:Disks Large Homolog 4 Protein; C000614189:Dlg1 protein, mouse; C501119:Dlg1 protein, rat; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D000074407:SAP90-PSD95 Associated Proteins; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases