Phosphorylation of cysteine string protein on Serine 10 triggers 14-3-3 protein binding

Gerald R. Prescott, Rosalind E. Jenkins, Ciara M. Walsh, Alan Morgan

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Cysteine string Protein (CSP) is a neuronal chaperone that maintains normal neurotransmitter exocytosis and is essential for preventing presynaptic neuroclegeneration. CSP is phosphorylated in vivo on a single residue, Ser10, and this phosphorylation regulates its cellular functions, although the molecular mechanisms involved are unclear. To identify novel phosphorylation-specific binding partners for CSP, we used a pull-down approach using synthetic peptides and recombinant proteins. A single protein band was observed to bind specifically to a Ser10-phosphorylated CSP peptide (residues 4-14) compared to a non-phosphorylated peptide. This band was identified as 14-3-3 protein of various isoforms using mass spectrometry and Western blotting. PKA phosphorylation of full-length CSP protein Stimulated 14-3-3 binding, and this was abolished in a Ser10-Ala mutant CSP, confirming the binding site as phospho-Ser10. As both CSP and 14-3-3 proteins are implicated in neurotransmitter exocytosis and neurodegeneration, this novel phosphorylation-dependent interaction may help maintain the functional integrity of the synapse. (C) 2008 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)809-814
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume377
Issue number3
DOIs
Publication statusPublished - 19 Dec 2008

Keywords

  • Neurodegeneration
  • Exocytosis
  • Synapse
  • Chaperone
  • Protein kinase A
  • Akt
  • ADRENAL CHROMAFFIN CELLS
  • ALPHA-SYNUCLEIN
  • REGULATED EXOCYTOSIS
  • NEUROTRANSMITTER EXOCYTOSIS
  • MOLECULAR CHAPERONE
  • CALCIUM SENSITIVITY
  • CSP-ALPHA
  • DROSOPHILA
  • 14-3-3-PROTEINS
  • BRAIN

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