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

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

Research output: Contribution to journalArticle

71 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Synaptotagmin I
Phosphatidylinositol Phosphates
Phospholipids
Polyphosphates
Phosphatidylinositols
Mutation
Modulators
Neurotransmitter Agents
C2 Domains

ASJC Scopus subject areas

  • Biochemistry

Cite this

Li, L., Shin, O. H., Rhee, J. S., Araç, D., Rah, J. C., Rizo, J., ... 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

Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1. / Li, LiYi; Shin, Ok Ho; Rhee, Jeong Seop; Araç, Demet; Rah, Jong Cheol; Rizo, Josep; Südhof, Thomas; Rosenmund, Christian.

In: Journal of Biological Chemistry, Vol. 281, No. 23, 09.06.2006, p. 15845-15852.

Research output: Contribution to journalArticle

Li, L, Shin, OH, Rhee, JS, Araç, D, Rah, JC, 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, vol. 281, no. 23, pp. 15845-15852. https://doi.org/10.1074/jbc.M600888200
Li, LiYi ; Shin, Ok Ho ; Rhee, Jeong Seop ; Araç, Demet ; Rah, Jong Cheol ; Rizo, Josep ; Südhof, Thomas ; Rosenmund, Christian. / Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 23. pp. 15845-15852.
@article{782cf5d1324f4c83921c568e06740f39,
title = "Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1",
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.",
author = "LiYi Li and Shin, {Ok Ho} and Rhee, {Jeong Seop} and Demet Ara{\cc} and Rah, {Jong Cheol} and Josep Rizo and Thomas S{\"u}dhof and Christian Rosenmund",
year = "2006",
month = "6",
day = "9",
doi = "10.1074/jbc.M600888200",
language = "English (US)",
volume = "281",
pages = "15845--15852",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "23",

}

TY - JOUR

T1 - Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1

AU - Li, LiYi

AU - Shin, Ok Ho

AU - Rhee, Jeong Seop

AU - Araç, Demet

AU - Rah, Jong Cheol

AU - Rizo, Josep

AU - Südhof, Thomas

AU - Rosenmund, Christian

PY - 2006/6/9

Y1 - 2006/6/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33744921671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33744921671&partnerID=8YFLogxK

U2 - 10.1074/jbc.M600888200

DO - 10.1074/jbc.M600888200

M3 - Article

C2 - 16595652

AN - SCOPUS:33744921671

VL - 281

SP - 15845

EP - 15852

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 23

ER -