Structure of a novel InsP3 receptor.
Inositol 1,4,5-trisphosphate (InsP3) constitutes a major intracellular second messenger that transduces many growth factor and neurotransmitter signals. InsP3 causes the release of Ca2+ from intracellular stores by binding to specific receptors that are coupled to Ca2+ channels. One such receptor from cerebellum has previously been extensively characterized. We have now determined the full structure of a second, novel InsP3 receptor which we refer to as type 2 InsP3 receptor as opposed to the cerebellar type 1 InsP3 receptor. The type 2 InsP3 receptor has the same general structural design as the cerebellar type 1 InsP3 receptor with which it shares 69% sequence identity. Expression of the amino-terminal 1078 amino acids of the type 2 receptor demonstrates high affinity binding of InsP3 to the type 2 receptor with a similar specificity but higher affinity than observed for the type 1 receptor. These results demonstrate the presence of several types of InsP3 receptor in brain and raise the possibility that intracellular Ca2+ signaling may involve multiple pathways with different regulatory properties dependent on different InsP3 receptors.
Südhof
T C
TC
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Newton
C L
CL
Archer
B T
BT
Ushkaryov
Y A
YA
Mignery
G A
GA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels; D004247:DNA / Q000235:genetics; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D016415:Sequence Alignment; D013379:Substrate Specificity
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA; D002118:Calcium