title: The role of Ca2+ signaling in cell function with special reference to exocrine secretion.
abstract: Inositol 1,4,5-trisphosphate (IP3) is a second messenger that induces the release of calcium from the endoplasmic reticulum (ER). The IP3 receptor was discovered as a developmentally regulated glycophosphoprotein, P400, that is absent in strains of mutant mice. The crystal structures of the IP3-binding core and N-terminal suppressor sequence of the IP3 receptor have been identified. The IP3-binding core's affinity to IP3 is similar among the three isoforms of IP3 receptors; however, the N-terminal IP3-binding suppressor region is responsible for isoform-specific IP3-binding affinity tuning. Various pathways for the trafficking of IP3 receptors have been identified; for example, the ER forms a meshwork on which IP3 receptors move by lateral diffusion, and vesicular ER subcompartments containing IP3 receptors move rapidly along microtubules using a kinesin motor. Furthermore, IP3 receptor messenger RNA within messenger RNA granules also moves along microtubules. Recently, we discovered that IP3 receptors play a crucial role in exocrine secretion. ERp44 works as a redox sensor in the ER and regulates IP3 type 1 receptor activity. IP3 receptor also releases IP3 receptor-binding protein released with IP3 (IRBIT). IRBIT is a pseudoligand for IP3 that regulates the frequency and amplitude of calcium oscillations through the IP3 receptor. IRBIT binds to pancreas-type sodium bicarbonate cotransporter 1, which is important for acid-base balance. Type 2 and 3 double-deficient mice show a deficit in saliva and lacrimal and pancreatic juice secretion. Type 1 IP3 receptor influences brain-derived neurotrophic factor production.
authors.affiliation: Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, Japan. mikosiba@brain.riken.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hisatsune
authors.forename: Akira
authors.initials: A
authors.lastname: Futatsugi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Mizutani
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Kiyomitsu
authors.initials: K
authors.lastname: Miyachi
mesh_terms: D043383:Adenosylhomocysteinase / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology; D005088:Exocrine Glands / Q000378:metabolism*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice / Q000196:embryology; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D043383:Adenosylhomocysteinase; C510392:IRBIT protein, mouse