Ion channel clustering by membrane-associated guanylate kinases: Differential regulation by N-terminal lipid and metal binding motifs

Alaa E. El-Husseini, J. Rick Topinka, Joshua E. Lehrer-Graiwer, Bonnie L. Firestein, Sarah E. Craven, Chiye Aoki, David S. Bred

Research output: Contribution to journalArticlepeer-review

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-192 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.

Original languageEnglish (US)
Pages (from-to)23904-23910
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number31
DOIs
StatePublished - Aug 4 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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