Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein.
NMDA receptors interact directly with postsynaptic density-95 (PSD-95), a scaffold protein that organizes a cytoskeletal- signaling complex at the postsynaptic membrane. The molecular mechanism by which the PSD-95-based protein complex is trafficked to the postsynaptic site is unknown but presumably involves specific motor proteins. Here we demonstrate a direct interaction between the PSD-95-associated protein guanylate kinase domain-associated protein (GKAP) and dynein light chain (DLC), a light chain subunit shared by myosin-V (an actin-based motor) and cytoplasmic dynein (a microtubule-based motor). A yeast two-hybrid screen with GKAP isolated DLC2, a novel protein 93% identical to the previously cloned 8 kDa dynein light chain (DLC1). A complex containing PSD-95, GKAP, DLC, and myosin-V can be immunoprecipitated from rat brain extracts. DLC colocalizes with PSD-95 and F-actin in dendritic spines of cultured neurons and is enriched in biochemical purifications of PSD. Immunogold electron microscopy reveals a concentration of DLC in the postsynaptic compartment of asymmetric synapses of brain in which it is associated with the PSD and the spine apparatus. We discuss the possibility that the GKAP/DLC interaction may be involved in trafficking of the PSD-95 complex by motor proteins.
Pubmed ID: 10844022 RIS Download
Amino Acid Sequence | Animals | Binding Sites | Brain | Calmodulin-Binding Proteins | Cells, Cultured | Cerebral Cortex | Cloning, Molecular | Consensus Sequence | Dyneins | Embryo, Mammalian | Guanylate Kinase | Hippocampus | Humans | Intracellular Signaling Peptides and Proteins | Macromolecular Substances | Membrane Proteins | Molecular Sequence Data | Myosin Light Chains | Myosin Type V | Nerve Tissue Proteins | Neurons | Nucleoside-Phosphate Kinase | Rats | Recombinant Proteins | Saccharomyces cerevisiae | Sequence Alignment | Sequence Homology, Amino Acid | Spinal Cord | Synapses