Cytosolic Multiple Inositol Polyphosphate Phosphatase in the Regulation of Cytoplasmic Free Ca2+ Concentration

Jia Yu, Barbara Leibiger, Shao Nian Yang, James J. Caffery, Stephen B. Shears, Ingo B. Leibiger, Christopher J. Barker, Per Olof Berggren

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Multiple inositol polyphosphate phosphatase (MIPP) is an enzyme that, in vitro, has the interesting property of degrading higher inositol polyphosphates to the Ca2+ second messenger, inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), independently of inositol lipid breakdown. We hypothesized that a truncated cytosolic form of the largely endoplasmic reticulum-confined MIPP (cyt-MIPP) could represent an important new tool in the investigation of Ins(1,4,5)P3-dependent intracellular Ca 2+ homeostasis. To optimize our ability to judge the impact of cyt-MIPP on intracellular Ca2+ concentration ([Ca2+] i) we chose a poorly responsive β-cell line (HIT M2.2.2) with an abnormally low [Ca2+]i. Our results show for the first time in an intact mammalian cell that cyt-MIPP expression leads to a significant enhancement of Ins(1,4,5)P3 concentration. This is achieved without a significant interference from other cyt-MIPP-derived inositol phosphates. Furthermore, the low basal [Ca2+]i of these cells was raised to normal levels (35 to 115 nm) when they expressed cyt-MIPP. Noteworthy is that the normal feeble glucose-induced Ca2+ response of HIT M2.2.2 cells was enhanced dramatically by mechanisms related to this increase in basal [Ca2+]i. These data support the use of cyt-MIPP as an important tool in investigating Ins(1,4,5)P 3-dependent Ca2+ homeostasis and suggest a close link between Ins(1,4,5)P3 concentration and basal [Ca2+] i, the latter being an important modulator of Ca2+ signaling in the pancreatic β-cell.

Original languageEnglish (US)
Pages (from-to)46210-46218
Number of pages9
JournalJournal of Biological Chemistry
Issue number47
StatePublished - Nov 21 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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