Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1

Li Yi Li, Ok Ho Shin, Jeong Seop Rhee, Demet Araç, Jong Cheol Rah, Josep Rizo, Thomas Südhof, Christian Rosenmund

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Ca2+-dependent phospholipid binding to the C2A and C2B domains of synaptotagmin 1 is thought to trigger fast neurotransmitter release, but only Ca2+ binding to the C2B domain is essential for release. To investigate the underlying mechanism, we have compared the role of basic residues in Ca2+/phospholipid binding and in release. Mutations in a polybasic sequenceonthe side of the C 2B domain β-sandwich or in a basic residue in a top Ca 2+-binding loop of the C2A domain (R233) cause comparable decreases in the apparent Ca2+ affinity of synaptotagmin 1 and the Ca2+ sensitivity of release, whereas mutation of the residue homologous to Arg233 in the C2B domain (Lys366) has no effect. Phosphatidylinositol polyphosphates co-activate Ca 2+-dependent and -independent phospholipid binding to synaptotagmin 1, but the effects of these mutations on release only correlate with their effects on the Ca2+-dependent component. These results reveal clear distinctions in the Ca2+-dependent phospholipid binding modes of the synaptotagmin 1 C2 domains that may underlie their functional asymmetry and suggest that phosphatidylinositol polyphosphates may serve as physiological modulators of Ca2+ affinity of synaptotagmin 1 in vivo.

Original languageEnglish (US)
Pages (from-to)15845-15852
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number23
DOIs
StatePublished - Jun 9 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Phosphatidylinositol phosphates as co-activators of Ca<sup>2+</sup> binding to C<sub>2</sub> domains of synaptotagmin 1'. Together they form a unique fingerprint.

  • Cite this

    Li, L. Y., Shin, O. H., Rhee, J. S., Araç, D., Rah, J. C., Rizo, J., Südhof, T., & Rosenmund, C. (2006). Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1. Journal of Biological Chemistry, 281(23), 15845-15852. https://doi.org/10.1074/jbc.M600888200