Disease relevance of Itp-r83A

• Here we describe the development of a baculovirus (BV)/Sf (S. frugiperda) cell system that can be used to look at IP3R function [1].

Psychiatry related information on Itp-r83A

• Coupled with our earlier observation that an itpr homozygous null allele dies at the second instar stage, it appears that there is a critical period for itpr gene function in second instar larvae [2].

High impact information on Itp-r83A

• To study the role of the IP3 receptor (IP3R) upon egg activation, cDNA clones encoding IP3R expressed in the Xenopus oocytes were isolated [3].
• Active PLC hydrolyzes phosphatidylinositol bisphosphate (PIP2) into the two second messengers inositol 1,4,5-trisphosphate (InsP3) and diacyl glycerol (DAG) [4].
• Constructs that chelate InsP3 also prevent nuclear division [5].
• The transient receptor potential protein (Trp) is a putative capacitative Ca2+ entry channel present in fly photoreceptors, which use the inositol 1,4,5-trisphosphate (InsP3) signaling pathway for phototransduction [6].
• The spatial distribution of the signaling complex argues against a direct conformational coupling of Trp to an InsP3 receptor supposed to be present in the membrane of internal photoreceptor Ca2+ stores [6].

Biological context of Itp-r83A

• Here we show that mutants for adenylate cyclase (rut) synergize, during larval molting, with itpr mutant alleles, indicating that both cAMP and InsP(3) signaling pathways function in this process [7].
• The Drosophila InsP3R gene is located at the region 83A5-9 on the third chromosome and expresses throughout development but predominantly in the adult [8].
• Ca(2+) is released from intracellular stores by binding of inositol trisphosphate (IP3) to the IP3 receptor (IP3R), yet no clear role in cytokinesis has been established for the precursor of IP3, phosphatidylinositol 4,5-bisphosphate (PIP2) [9].
• The gene has a total of 11 introns, of which more than half are clustered in a region of the modulatory domain of the IP3R [10].
• All mutant phenotypes are rescued by expression of an itpr(+) transgene in serotonin and dopamine neurons [11].

Anatomical context of Itp-r83A

• IP3 binding to its receptor (IP3R) triggers Ca(2+) release from the endoplasmic reticulum (ER) to the cytosol, whereas IP4 physiological role remains elusive [12].
• The expressed levels of dGqalpha and itpr in the tarsus of poxn70 mutant flies were reduced compared with those of wild-type flies [13].
• In addition, the InsP3R mRNA is abundant in the legs and thorax, which are enriched with a muscular system [8].
• InsP3 caused a significant stimulation of Mn2+ inflow in TRPL but not in mock oocytes [14].
• We correlated the results obtained in planar lipid bilayer experiments with measurements of InsP(3)-induced Ca(2+) fluxes in microsomes isolated from wild-type and heterozygous itpr mutants [15].

Associations of Itp-r83A with chemical compounds

• NorpA and itpr mutants reveal roles for phospholipase C and inositol (1,4,5)- trisphosphate receptor in Drosophila melanogaster renal function [16].
• The inositol (1,4,5)-trisphosphate receptors (InsP3R) are the intracellular calcium (Ca2+) release channels that play a key role in Ca2+ signaling in cells [17].
• Inositol 1,4,5-trisphosphate (IP3), generated by phosphoinositide (PI) hydrolysis, binds to and gates an intracellular Ca2+ channel, the IP3 receptor (IP3R), which is therefore a central component of this signaling cascade [1].
• Application of the cholinergic agonist carbamylcholine (100 microM) to transfected S2-DM1 cells expressing a Drosophila muscarinic acetylcholine receptor (DM1) emptied the InsP3-sensitive Ca2+ store but failed to affect the amplitude of alkalinization-evoked Ca2+ release [18].

Regulatory relationships of Itp-r83A

• Drosokinin-stimulated fluid transport is also reduced in homozygous and heteroallelic itpr mutants [16].
• In oocytes incubated in the presence of PMA (to suppress Ca2+ inflow through endogenous receptor-activated Ca2+ channels), the InsP3-induced stimulation of Ca2+ inflow through TRPL channels was more clearly evident than in oocytes incubated in the absence of PMA [14].

Other interactions of Itp-r83A

• Measurements of cytosolic calcium levels in intact tubules of wild-type and itpr mutants using targeted expression of the calcium reporter, aequorin, show that mutations in itpr attenuated both CAP(2b)- and Drosokinin-stimulated calcium responses [16].
• Here, we show that Drosophila mutants for the inositol 1,4,5-trisphosphate (InsP(3)) receptor gene (itpr) are flightless [11].
• Compensation of inositol 1,4,5-trisphosphate receptor function by altering sarco-endoplasmic reticulum calcium ATPase activity in the Drosophila flight circuit [19].

Analytical, diagnostic and therapeutic context of Itp-r83A

• Molecular cloning and characterization of the inositol 1,4,5-trisphosphate receptor in Drosophila melanogaster [8].
• Genetic dissection of itpr gene function reveals a vital requirement in aminergic cells of Drosophila larvae [2].
• Central to studies of IP metabolism is the essential development of efficient, fast, and reproducible methods for quantitative analysis of IPs in systems ranging from simple cell cultures to more complex tissues and whole organisms [20].

References