InsP3-mediated intracellular calcium signalling is altered by expression of synaptojanin-1

Biochem J. 2004 Sep 1;382(Pt 2):687-94. doi: 10.1042/BJ20040418.

Abstract

Phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] plays an important physiological role as a precursor for the InsP3-mediated intracellular calcium (Ca2+) signalling cascade. It also regulates membrane trafficking, actin function and transmembrane proteins. SJ-1 (synaptojanin-1), a phosphoinositide phosphatase, regulates the turnover of a PtdIns(4,5)P2 pool involved in clathrin and actin dynamics at the cell surface. We tested the interrelationship of this pool with PtdIns(4,5)P2 pools involved in Ca2+ signalling by expressing in Chinese-hamster ovary cells full-length SJ-1 or its 5-Pase (inositol 5-phosphatase) domain. SJ-1 significantly attenuated the generation of Ca2+ oscillations induced by ATP and the 5-Pase domain mimicked this effect. These changes correlated with increased PtdIns(4,5)P2 phosphatase activity of cellular extracts. Overexpression of the endoplasmic reticulum-anchored PtdIns(4)P phosphatase Sac1 did not affect Ca2+ oscillations, although it increased the Ca2+ efflux rate from intracellular stores. The ability of SJ-1 to alter intracellular Ca2+ signalling indicates a close functional interrelationship between plasma membrane PtdIns(4,5)P2 pools that control actin and endocytosis and those involved in the regulation of specific spatio-temporal Ca2+ signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / metabolism
  • Animals
  • CHO Cells / chemistry
  • CHO Cells / enzymology
  • CHO Cells / metabolism
  • Calcium / metabolism
  • Calcium Signaling / physiology*
  • Catalytic Domain / physiology
  • Cell Line
  • Cricetinae
  • Endoplasmic Reticulum / enzymology
  • Inositol 1,4,5-Trisphosphate / physiology*
  • Inositol Polyphosphate 5-Phosphatases
  • Intracellular Space / chemistry
  • Intracellular Space / enzymology
  • Intracellular Space / metabolism
  • Membrane Proteins / biosynthesis
  • Nerve Tissue Proteins / biosynthesis*
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphoric Monoester Hydrolases / biosynthesis*
  • Phosphoric Monoester Hydrolases / metabolism

Substances

  • Membrane Proteins
  • Nerve Tissue Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates
  • Sac1 protein, mammalian
  • Inositol 1,4,5-Trisphosphate
  • Adenosine Triphosphate
  • synaptojanin
  • Phosphoric Monoester Hydrolases
  • Inositol Polyphosphate 5-Phosphatases
  • Calcium