Research article summary (published 21 Jun 2009):

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

Full Abstract

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.

Author information

Author/s: Vasudevan, Lavanya (L); Jeromin, Andreas (A); Volpicelli-Daley, Laura (L); De Camilli, Pietro (P); Holowka, David (D); Baird, Barbara (B);

Affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.

Grants: R01-AI022449 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of cell science (J Cell Sci), published in England. (Language: eng)

Reference: 2009-Jul; vol 122 (issue Pt 14) : pp 2567-74

Dates: Created 2009/07/02; Completed 2009/09/17; Revised 2009/10/28;

PMID: 19549683, status: MEDLINE (last retrieved date: 10/29/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Antigens - metabolism Bone Marrow Cells - enzymology Calcium Signaling - drug effects Cell Line, Tumor Cell Membrane - enzymology Endoplasmic Reticulum - enzymology Enzyme Inhibitors - pharmacology Isoenzymes Mast Cells - drug effects; enzymology Mice Mice, Knockout

Mice, Knockout Phosphatidylinositol 4,5-Diphosphate - metabolism Phospholipase C gamma - metabolism Phosphoric Monoester Hydrolases - metabolism Phosphotransferases (Alcohol Group Acceptor) - deficiency; genetics; metabolism Rats Receptors, IgE - metabolism Recombinant Fusion Proteins - metabolism Sarcoplasmic Reticulum Calcium-Transporting ATPases - antagonists & inhibitors; metabolism Thapsigargin - pharmacology Time Factors Transfection

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Antigens (0) ; Enzyme Inhibitors (0) ; Isoenzymes (0) ; Phosphatidylinositol 4,5-Diphosphate (0) ; Receptors, IgE (0) ; Recombinant Fusion Proteins (0) ; Thapsigargin (67526-95-8) ; Phosphotransferases (Alcohol Group Acceptor) (EC 2.7.1.-) ; 1-phosphatidylinositol-4-phosphate 5-kinase (EC 2.7.1.68) ; Phosphoric Monoester Hydrolases (EC 3.1.3.-) ; inositol-1,4,5-trisphosphate 5-phosphatase (EC 3.1.3.56) ; Phospholipase C gamma (EC 3.1.4.3) ; Sarcoplasmic Reticulum Calcium-Transporting ATPases (EC 3.6.3.8)

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