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 journalArticle

18 Citations (Scopus)

Abstract

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
Pages (from-to)46210-46218
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number47
DOIs
StatePublished - Nov 21 2003
Externally publishedYes

Fingerprint

Inositol
Homeostasis
Cells
Polyphosphates
Inositol 1,4,5-Trisphosphate
Inositol Phosphates
multiple inositol-polyphosphate phosphatase
Second Messenger Systems
Endoplasmic Reticulum
Modulators
Lipids
Glucose
Cell Line
Enzymes
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry

Cite this

Yu, J., Leibiger, B., Yang, S. N., Caffery, J. J., Shears, S. B., Leibiger, I. B., ... Berggren, P. O. (2003). Cytosolic Multiple Inositol Polyphosphate Phosphatase in the Regulation of Cytoplasmic Free Ca2+ Concentration. Journal of Biological Chemistry, 278(47), 46210-46218. https://doi.org/10.1074/jbc.M303743200

Cytosolic Multiple Inositol Polyphosphate Phosphatase in the Regulation of Cytoplasmic Free Ca2+ Concentration. / Yu, Jia; Leibiger, Barbara; Yang, Shao Nian; Caffery, James J.; Shears, Stephen B.; Leibiger, Ingo B.; Barker, Christopher J.; Berggren, Per Olof.

In: Journal of Biological Chemistry, Vol. 278, No. 47, 21.11.2003, p. 46210-46218.

Research output: Contribution to journalArticle

Yu, J, Leibiger, B, Yang, SN, Caffery, JJ, Shears, SB, Leibiger, IB, Barker, CJ & Berggren, PO 2003, 'Cytosolic Multiple Inositol Polyphosphate Phosphatase in the Regulation of Cytoplasmic Free Ca2+ Concentration', Journal of Biological Chemistry, vol. 278, no. 47, pp. 46210-46218. https://doi.org/10.1074/jbc.M303743200
Yu, Jia ; Leibiger, Barbara ; Yang, Shao Nian ; Caffery, James J. ; Shears, Stephen B. ; Leibiger, Ingo B. ; Barker, Christopher J. ; Berggren, Per Olof. / Cytosolic Multiple Inositol Polyphosphate Phosphatase in the Regulation of Cytoplasmic Free Ca2+ Concentration. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 47. pp. 46210-46218.
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