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. CONCLUSION: 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.
Pubmed ID: 9286858 RIS Download
Adaptor Proteins, Signal Transducing | Adenomatous Polyposis Coli Protein | Amino Acid Sequence | Animals | Apoptosis Regulatory Proteins | Binding Sites | Brain | Cerebellum | Cloning, Molecular | Cytoskeletal Proteins | Guanylate Kinases | Hippocampus | Humans | Intracellular Signaling Peptides and Proteins | Male | Membrane Proteins | Mice | Microscopy, Immunoelectron | Molecular Sequence Data | Nerve Tissue Proteins | Neurons | Nucleoside-Phosphate Kinase | Precipitin Tests | Proteins | Rabbits | Rats | Receptors, N-Methyl-D-Aspartate | Repetitive Sequences, Nucleic Acid | Sequence Homology, Amino Acid