The inositol 1,4,5-trisphosphate receptor (InsP(3)R) forms ligand-regulated intracellular Ca(2+) release channels in the endoplasmic reticulum of all mammalian cells. The InsP(3)R has been suggested to have six transmembrane regions (TMRs) near its carboxyl terminus. A TMR-deletion mutation strategy was applied to define the location of the InsP(3)R pore. Mutant InsP(3)Rs were expressed in COS-...

BACKGROUND The Inositol 1,4,5-trisphosphate receptor (InsP(3)R) is an InsP(3) gated intracellular Ca(2+)-release channel. Characterization of Drosophila mutants for the InsP(3)R has demonstrated that InsP(3)-mediated Ca(2+) release is required in Drosophila larvae for growth and viability. METHODOLOGY/PRINCIPAL FINDINGS To understand the molecular basis of these growth defects a genome wide m...

Only one HAP1 isoform has been identified in humans, and this Vancouver, British Columbia Canada is most similar to rodent HAP1A (Li et al., 1998b). Association of HAP1 with hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) (Li et al., 2002), the p150Glued subunit of dynactin (Engelender et al., 1997; Summary Li et al., 1998a), and the Rac1 guanine nucleotide exchange factor Ka...

Inositol pyrophosphates (PP-InsPs) are highly phosphorylated molecules that have emerged as central nutrient messengers in eukaryotic organisms. They can bind to structurally diverse target proteins regulate biological functions, such protein–protein interactions. PP-InsPs strongly negatively charged and interact with basic surface patches proteins, making their quantitative biochemical analysi...

Synaptically released glutamate evokes slow IPSPs mediated by metabotropic glutamate receptors (mGluRs) in midbrain dopamine neurons. These mGluR IPSPs are caused by release of Ca(2+) from intracellular stores and subsequent activation of small-conductance Ca(2+)-activated K(+) channels (SK channels). To further investigate the intracellular mechanisms involved, the effect of photolyzing intrac...

Glycogenolytic agonists induce coordinated Ca(2+) oscillations in multicellular rat hepatocyte systems as well as in the intact liver. The coordination of intercellular Ca(2+) signals requires functional gap-junction coupling. The mechanisms ensuring this coordination are not precisely known. We investigated possible roles of Ca(2+) or inositol 1,4,5-trisphosphate (InsP(3)) as a coordinating me...

Inositol pyrophosphate diphosphoinositol pentakisphosphate is ubiquitously present in mammalian cells and contains highly energetic pyrophosphate bonds. We have previously reported that inositol hexakisphosphate kinase type 2 (InsP(6)K2), which converts inositol hexakisphosphate to inositol pyrophosphate diphosphoinositol pentakisphosphate, mediates apoptotic cell death via its translocation fr...

The inositol 1,4,5-trisphosphate (InsP 3 )-gated Ca channel in cerebellum is tightly regulated by Ca (Bezprozvanny, I., J. Watras, and B.E. Ehrlich. 1991. Nature (Lond.). 351:751–754; Finch, E.A., T.J. Turner, and S.M. Goldin. 1991. Science (Wash. DC). 252:443–446; Hannaert-Merah, Z., J.F. Coquil, L. Combettes, M. Claret, J.P. Mauger, and P. Champeil. 1994. J. Biol. Chem. 269:29642–29649; Iino,...

InsP(3) binding to type-1, but not type-3, InsP(3) receptors is inhibited by calmodulin in a Ca(2+)-independent fashion [Cardy and Taylor (1998) Biochem. J. 334, 447-455], and Ca(2+) mobilization by type-1 InsP(3) receptors of cerebellum is inhibited by calmodulin [Patel, Morris, Adkins, O'Beirne and Taylor (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 11627-11632]. Using cell types expressing predo...

Cardiac hypertrophy is associated with profound remodeling of Ca(2+) signaling pathways. During the early, compensated stages of hypertrophy, Ca(2+) fluxes may be enhanced to facilitate greater contraction, whereas as the hypertrophic heart decompensates, Ca(2+) homeostatic mechanisms are dysregulated leading to decreased contractility, arrhythmia and death. Although ryanodine receptor Ca(2+) r...