Role of IP3 receptor signaling in cell functions and diseases

Adv Biol Regul. 2015 Jan;57:217-27. doi: 10.1016/j.jbior.2014.10.001. Epub 2014 Oct 23.

Abstract

IP3 receptor (IP3R) was found to release Ca(2+) from non-mitochondrial store but the exact localization and the mode of action of IP3 remained a mystery. IP3R was identified to be P400 protein, a protein, which was missing in the cerebellum of ataxic mutant mice lacking Ca(2+) spikes in Pukinje cells. IP3R was an IP3 binding protein and was a Ca(2+) channel localized on the endoplasmic reticulum. Full-length cDNA of IP3R type 1 was initially cloned and later two other isoforms of IP3R (IP3R type 2 and type 3) were cloned in vertebrates. Interestingly, the phosphorylation sites, splicing sites, associated molecules, IP3 binding affinity and 5' promoter sequences of each isoform were different. Thus each isoform of IP3 receptor plays a role as a signaling hub offering a unique platform for matching various functional molecules that determines different trajectories of cell signaling. Because of this distinct role of each isoform of IP3R, the dysregulation of IP3 receptor causes various kinds of diseases in human and rodents such as ataxia, vulnerability to neuronal degeneration, heart disease, exocrine secretion deficit, taste perception deficit. Moreover, IP3 was found not only to release Ca(2+), but also to release IRBIT (IP3receptor binding protein released with inositol trisphosphate) essential for the regulation of acid-base balance, RNA synthesis and ribonucleotide reductase.

Keywords: 2-APB; Ataxia; Ca(2+); Calcium oscillation; IP(3) receptor; IRBIT; Malaria; P400; Signaling hub; Trypanosoma cruzi.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosylhomocysteinase / genetics
  • Adenosylhomocysteinase / metabolism
  • Animals
  • Ataxia* / genetics
  • Ataxia* / metabolism
  • Ataxia* / pathology
  • Calcium Signaling / genetics*
  • Heart Diseases* / genetics
  • Heart Diseases* / metabolism
  • Heart Diseases* / pathology
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors* / genetics
  • Inositol 1,4,5-Trisphosphate Receptors* / metabolism
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Neurodegenerative Diseases* / genetics
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Purkinje Cells / metabolism
  • Purkinje Cells / pathology
  • Taste Perception / genetics

Substances

  • CLECL1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Lectins, C-Type
  • Membrane Proteins
  • Adenosylhomocysteinase
  • IRBIT protein, mouse