Disease relevance of Itpr3

• In the present study, we show that thimerosal potentiated IICR (IP3-induced Ca2+ release) and IP3-binding activity of IP3R1, expressed in triple IP3R-knockout R23-11 cells derived from DT40 chicken B lymphoma cells, but not of IP3R3 or [D1-225]-IP3R1, which lacks the N-terminal suppressor domain [1].

High impact information on Itpr3

• Similar results were obtained with an IP3R-3 mutant carrying a conservative point mutation in the selectivity filter region of the channel (D2477E); however, an IP3R-3 mutant in which this same aspartate was replaced by alanine (D2477A) failed to restore either BCR-induced Ca2+ release or receptor-dependent Ba2+ entry [2].
• We have confirmed the expression of IP3R-3 in pancreatic islets by immunohistocytochemistry and localized this protein to the secretory granules of insulin-secreting beta cells and somatostatin-secreting delta cells by immunogold electron microscopy [3].
• Secretory granules contain high levels of Ca2+, and the presence of IP3R-3 in the granule provides a mechanism for mobilizing granule Ca2+ stores in response to glucose and/or hormones [3].
• The localization of IP3R-3 to secretory granules of insulin-secreting beta cells and somatostatin-secreting delta cells suggests that granule Ca2+ stores actively participate in the secretory process and that their release is regulated by inositol 1,4,5-trisphosphate [3].
• The regulation of IP3R-3 levels by glucose, diabetes, and refeeding may allow the beta cell to adjust the insulin secretory response to changing physiological conditions [3].

Biological context of Itpr3

• The predominant expression of the type-3 InsP3 receptor in the bronchial mucosa may be part of a mechanism coping with oxidative stress in that tissue [4].
• Type 3 inositol 1,4,5-trisphosphate receptor modulates cell death [5].
• Upon cell differentiation, induced by culturing the cells on Matrigel, the expression pattern of the IP3R changed even further in all endothelial cell types: IP3R-1 was reduced in all three cell kinds, while IP3R-3 raised significantly in RAEC and RAMEC [6].

Anatomical context of Itpr3

• Reverse transcriptase-polymerase chain reaction amplification of IP3R-1, -2, and -3 mRNAs in adult rat pancreatic islets indicated that IP3R-3 was the predominant subtype expressed in this tissue and thus may be responsible for mediating the effects of IP3 on insulin secretion [7].
• Immunohistocytochemical studies of cells expressing recombinant IP3R-3 indicated that it has a preferential cellular distribution in the endoplasmic reticulum [7].
• The IP3R-3 is also expressed in adult pancreatic islets, kidney, gastrointestinal tract, and brain [7].
• RNA and protein blotting studies indicate that IP3R-3 is expressed in a number of different cultured cell lines including insulin-secreting RINm5F cells [7].
• Expression of recombinant rat IP3R-3 in COS-7 cells showed that it bound IP3 as well as inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate [7].

Associations of Itpr3 with chemical compounds

• Sequence and functional characterization of a third inositol trisphosphate receptor subtype, IP3R-3, expressed in pancreatic islets, kidney, gastrointestinal tract, and other tissues [7].
• This interaction was not found for IP3R3, in agreement with the lack of functional stimulation of this isoform by thimerosal [1].

Regulatory relationships of Itpr3

• Furthermore, we showed by double-immunolabeling methods that P2Y1-expressing cells coexpressed both IP3R3 and SNAP-25 [8].

Other interactions of Itpr3

• We conclude that Ca2+ release mediated by the type-3 InsP3 receptor mainly differs from that mediated by the type-1 InsP3 receptor by its lack of stimulation by sulfhydryl oxidation and its lower ATP and InsP3 sensitivity [4].
• Three mammalian InsP3R isoforms--InsP3R type 1 (InsP3R1), InsP3R type 2 (InsP3R2), and InsP3R type 3 (InsP3R3) are expressed in mammals, but the functional differences between the three mammalian InsP3R isoforms are poorly understood [9].
• Western blotting was also performed with antibodies directed against GLUT1, glial fibrillary acidic protein, adaptin, IP3R-3, integrins alphav and collagen IV as controls to determine whether the preparations were contaminated by other membranes [10].
• CaM kinase II was found throughout the entire intracellular canalicular F-actin domain of parietal cells, whereas the type 3 InsP3 receptor was restricted to the neck region [11].

References