The beta- and gamma-isoforms of type I PIP5K regulate distinct stages of Ca2+ signaling in mast cells.


Journal Article

Crosslinking of IgE receptors by antigen initiates Ca2+ mobilization in mast cells by activating phospholipase-C gamma-mediated hydrolysis of phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2]. The resulting inositol 1,4,5-trisphosphate-mediated Ca2+ release from the endoplasmic reticulum (ER) activates store-operated Ca2+ entry, which is necessary for exocytotic release of inflammatory mediators. To investigate roles for PtdIns(4,5)P2-synthesizing isozymes of the type I phosphatidylinositol 4-phosphate 5-kinase family (PIP5K-I) in mast cell signaling, we compared the ectopic expression of wild-type and catalytically inactive PIP5K-I beta in RBL-2H3 mast cells. Surprisingly, both antigen and thapsigargin-stimulated Ca2+ influx were reduced by overexpression of active PIP5K-I beta, whereas antigen-stimulated Ca2+ release from ER stores was unaffected. Consistent with these results, Ca2+ entry stimulated by antigen or thapsigargin was enhanced by expression of a plasma-membrane-associated inositol polyphosphate 5'-phosphatase, whereas antigen-stimulated Ca2+ release from stores was reduced. To investigate the role of PIP5K-I gamma in antigen-stimulated Ca2+ mobilization, we used bone-marrow-derived mast cells from PIP5K-I gamma(-/-) mice. Antigen-stimulated Ca2+ release from ER stores was substantially reduced in the absence of PIP5K-I gamma, but thapsigargin-mediated Ca2+ entry was unaffected. In summary, PIP5K-I gamma positively regulates antigen-stimulated Ca2+ release from ER stores, whereas PIP5K-I beta negatively regulates store-operated Ca2+ entry, suggesting that these different PIP5K-I isoforms synthesize functionally distinct pools of PtdIns(4,5)P2 at the plasma membrane.

Full Text

Cited Authors

  • Vasudevan, L; Jeromin, A; Volpicelli-Daley, L; De Camilli, P; Holowka, D; Baird, B

Published Date

  • July 2009

Published In

Volume / Issue

  • 122 / Pt 14

Start / End Page

  • 2567 - 2574

PubMed ID

  • 19549683

Pubmed Central ID

  • 19549683

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.048124


  • eng