Synaptotagmin I is a molecular target for lead

Christopher M.L.S. Bouton, Laurence P. Frelin, Cameron E. Forde, Hilary Arnold Godwin, Jonathan Pevsner

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


Lead poisoning can cause a wide range of symptoms with particularly severe clinical effects on the CNS. Lead can increase spontaneous neurotransmitter release but decrease evoked neurotransmitter release. These effects may be caused by an interaction of lead with specific molecular targets involved in neurotransmitter release. We demonstrate here that the normally calcium-dependent binding characteristics of the synaptic vesicle protein synaptotagmin I are altered by lead. Nanomolar concentrations of lead induce the interaction of synaptotagmin I with phospholipid liposomes. The C2A domain of synaptotagmin I is required for lead-mediated phospholipid binding. Lead protects both recombinant and endogenous rat brain synaptotagmin I from proteolytic cleavage in a manner similar to calcium. However, lead is unable to promote the interaction of either recombinant or endogenous synaptotagmin I and syntaxin. Finally, nanomolar concentrations of lead are able to directly compete with and inhibit the ability of micromolar concentrations of calcium to induce the interaction of synaptotagmin I and syntaxin. Based on these findings, we conclude that synaptotagmin I may be an important, physiologically relevant target of lead.

Original languageEnglish (US)
Pages (from-to)1724-1735
Number of pages12
JournalJournal of Neurochemistry
Issue number6
StatePublished - 2001
Externally publishedYes


  • Calcium
  • Metal
  • Phospholipid
  • Poisoning
  • Syntaxin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Synaptotagmin I is a molecular target for lead'. Together they form a unique fingerprint.

Cite this