Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Animals
-
Cell Compartmentation
-
Cell Membrane / ultrastructure
-
Cerebral Cortex / cytology
-
Cerebral Cortex / metabolism
-
Disks Large Homolog 4 Protein
-
Fluorescent Antibody Technique
-
Guanylate Kinases
-
Hippocampus / cytology
-
Hippocampus / metabolism
-
Intracellular Signaling Peptides and Proteins
-
Ion Channels / metabolism*
-
Lipoproteins / metabolism*
-
Membrane Proteins / isolation & purification
-
Membrane Proteins / metabolism*
-
Nerve Tissue Proteins / isolation & purification
-
Nerve Tissue Proteins / metabolism*
-
Neuropeptides / isolation & purification
-
Neuropeptides / metabolism
-
Nucleoside-Phosphate Kinase / metabolism*
-
Palmitic Acid
-
Protein Processing, Post-Translational
-
Rats
-
Rats, Sprague-Dawley
-
Zinc / metabolism
Substances
-
Adaptor Proteins, Signal Transducing
-
Disks Large Homolog 4 Protein
-
Dlg1 protein, rat
-
Dlg3 protein, rat
-
Dlg4 protein, rat
-
Intracellular Signaling Peptides and Proteins
-
Ion Channels
-
Lipoproteins
-
Membrane Proteins
-
Mpp2 protein, rat
-
Nerve Tissue Proteins
-
Neuropeptides
-
postsynaptic density proteins
-
Palmitic Acid
-
Nucleoside-Phosphate Kinase
-
Guanylate Kinases
-
Zinc