Ion channel clustering by membrane-associated guanylate kinases. Differential regulation by N-terminal lipid and metal binding motifs.
Copyright policy )Ion channel clustering by membrane-associated guanylate kinases. Differential regulation by N-terminal lipid and metal binding motifs.
The postsynaptic density protein PSD-95 and related membrane-associated guanylate kinase (MAGUK) proteins assemble signal transduction complexes at sites of cell-cell contact including synapses. Whereas PSD-95 and PSD-93 occur only at postsynaptic sites in hippocampal neurons, SAP-102 also occurs in axons. In heterologous cells, PSD-95 and PSD-93 mediate cell surface ion channel clustering, but SAP-102 and SAP-97 do not. This selective ion channel clustering activity by MAGUKs is explained by differential palmitoylation, as PSD-93 and PSD-95 are palmitoylated though SAP-97, and SAP-102 are not. Rather than being palmitoylated, we find that N-terminal cysteines from SAP-102 tightly bind to zinc. And, appending the N terminus of SAP-102 to PSD-95 results in localization of the chimera to both axons and dendrites. These data suggest that lipid modifications and heavy metal associations with the N termini of MAGUKs mediate differential functions and subcellular localizations of these synaptic scaffolds.
Cerebral Cortex, Lipoproteins, Cell Membrane, Neuropeptides, Intracellular Signaling Peptides and Proteins, Palmitic Acid, Fluorescent Antibody Technique, Membrane Proteins, Nerve Tissue Proteins, Hippocampus, Ion Channels, Cell Compartmentation, Rats, Rats, Sprague-Dawley, Animals, Nucleoside-Phosphate Kinase, Disks Large Homolog 4 Protein, Guanylate Kinases, Protein Processing, Post-Translational, Adaptor Proteins, Signal Transducing
Cerebral Cortex, Lipoproteins, Cell Membrane, Neuropeptides, Intracellular Signaling Peptides and Proteins, Palmitic Acid, Fluorescent Antibody Technique, Membrane Proteins, Nerve Tissue Proteins, Hippocampus, Ion Channels, Cell Compartmentation, Rats, Rats, Sprague-Dawley, Animals, Nucleoside-Phosphate Kinase, Disks Large Homolog 4 Protein, Guanylate Kinases, Protein Processing, Post-Translational, Adaptor Proteins, Signal Transducing
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