[Intracellular calcium-releasing channels as cellular targets for immunophilins: a molecular, functional and structural analysis].
In this study, the FKBP12-binding properties of IP3Rs and RyRs were compared. Although the primary sequence of IP3Rs en RyRs contained a putative FKBP12-binding site, the functional, molecular and structural properties of these sites appeared to be completely different. For RyRs, FKBPs appear to function as associated proteins that are important for the functional regulation of the channel, thereby stabilizing the RyR complex. For IP3Rs, FKBPs might be involved in the de novo protein synthesis of the IP3Rs and the folding of the peptide chain to a functional IP3R protein, thereby functioning as helper enzymes. Hence, it is very unlikely that they function as associated regulatory proteins of the IP3R. In addition, we provided evidence that FKBP 12 is also an important regulating protein of the Ca(2+)-flux properties of the RyR3. FKBP12 clearly modulated both RyR3-mediated global and local Ca(2+)-responses.
Bultynck
G
G
Laboratorium voor Fysiologie, Faculteit Geneeskunde--KULeuven, Campus Gasthuisberg O/N, Herestraat 49-B 3000 Leuven.
Van Acker
K
K
Missiaen
L
L
Callewaert
G
G
Parys
J B
JB
De Smedt
H
H
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020104:Immunophilins / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008969:Molecular Sequence Data; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D022061:Tacrolimus Binding Protein 1A; D020104:Immunophilins; D002118:Calcium