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

Cysteine string protein (CSP) is a neuronal chaperone that maintains normal neurotransmitter exocytosis and is essential for preventing presynaptic neurodegeneration. CSP is phosphorylated in vivo on a single residue, Ser10, and this phosphorylation regulates its cellular functions, although the mol...

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Published inBiochemical and biophysical research communications Vol. 377; no. 3; pp. 809 - 814
Main Authors Prescott, Gerald R., Jenkins, Rosalind E., Walsh, Ciara M., Morgan, Alan
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 19.12.2008
Subjects
14-3-3 Proteins - genetics
14-3-3 Proteins - metabolism
Akt
Animals
Cattle
Cells, Cultured
Chaperone
Exocytosis
HSP40 Heat-Shock Proteins - genetics
HSP40 Heat-Shock Proteins - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
Neurodegeneration
Neurons - metabolism
Peptides - metabolism
Phosphorylation
Protein Binding
Protein kinase A
Rats
Serine - metabolism
Synapse
Protein kinase A
Synapse
Akt
Exocytosis
Neurodegeneration
Chaperone
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Summary:Cysteine string protein (CSP) is a neuronal chaperone that maintains normal neurotransmitter exocytosis and is essential for preventing presynaptic neurodegeneration. 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.
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ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2008.10.069