Binding of IRBIT to the IP3 receptor: determinants and functional effects.
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.
Devogelaere
Benoit
B
Laboratorium voor Fysiologie, Katholieke Universiteit Leuven Campus Gasthuisberg O/N1, Leuven, Belgium.
Nadif Kasri
Nael
N
Derua
Rita
R
Waelkens
Etienne
E
Callewaert
Geert
G
Missiaen
Ludwig
L
Parys
Jan B
JB
De Smedt
Humbert
H
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*
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