title: Binding of IRBIT to the IP3 receptor: determinants and functional effects.
abstract: IRBIT has previously been shown to interact with the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) in an IP3-sensitive way. So far it remained to be elucidated whether this interaction was direct or indirect, and whether it was functionally relevant. We now show that IRBIT can directly interact with the IP3R, and that both the suppressor domain and the IP3-binding core of the IP3R are essential for a strong interaction. Moreover, we identified a PEST motif and a PDZ-ligand on IRBIT which were critical for the interaction with the IP3R. Furthermore, we identified Asp-73 as a critical residue for this interaction. Finally, we demonstrated that this interaction functionally affects the IP3R: IRBIT inhibits both IP3 binding and IP3-induced Ca2+ release.
authors.affiliation: Laboratorium voor Fysiologie, Katholieke Universiteit Leuven Campus Gasthuisberg O/N1, Leuven, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Devogelaere
authors.forename: Nael
authors.initials: N
authors.lastname: Nadif Kasri
authors.forename: Rita
authors.initials: R
authors.lastname: Derua
authors.forename: Etienne
authors.initials: E
authors.lastname: Waelkens
authors.forename: Geert
authors.initials: G
authors.lastname: Callewaert
authors.forename: Ludwig
authors.initials: L
authors.lastname: Missiaen
authors.forename: Jan B
authors.initials: JB
authors.lastname: Parys
authors.forename: Humbert
authors.initials: H
authors.lastname: De Smedt
mesh_terms: D043383:Adenosylhomocysteinase / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D002417:Cattle; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D018398:Homeodomain Proteins; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007295:Inositol Phosphates; D018160:Receptors, Cytoplasmic and Nuclear; C052128:inositol 3-phosphate; D043383:Adenosylhomocysteinase; C510392:IRBIT protein, mouse