By Novartis Foundation
This publication brings jointly contributions from key investigators within the sector of temporary Receptor power (TRP) channel constitution and serve as. It covers the constitution, functionality and law of mammalian TRP channels and mechanisms of sign transduction. The discussions point out study that may increase realizing of the position of TRP channels in common mobile body structure, the involvement of TRP channels in disorder states and their capability use as molecular goals for novel healing brokers.
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Extra resources for Mammalian TRP Channels as Molecular Targets (Novartis Foundation Symposium 258)
Schilling: Unlike FKBP-12 which has only a single FK506 binding site, FKBP59 is thought to have up to three binding domains. We have cut FKBP-59 into three pieces corresponding to the individual FK506 binding domains to determine which domain actually interacts with INAD or the channel protein, and which domains have functional e¡ects on channel activity. Scharenberg: Actually, someone has made a dimer of FK506. They call it FK1012, and they use it as a chemical dimerizer. Penner: Bill, is your interpretation of the FK506 data on the channel that it displaces FKBP, and then inhibits it?
In in vitro binding studies, CaM and a TRPC-binding IP3R fragment competed for binding to TRPC. Using patch clamp techniques, we showed that TRPC3 and TRPC4 were activated by a peptide representing the TRPC-binding domain of IP3R3 and also by inactivation of CaM. The TRPC3 activity is sensitive to inhibition by Ca2+ and CaM. We conclude that a direct interaction between IP3R and TRPC is involved in the activation of TRPCformed channels and such activation is achieved through displacement of the inhibitory CaM from a common binding site located at the C-terminus of TRPC.
Scharenberg: Have any FKBPs come up in the genetic screens of Drosophila phototransduction mutants? Montell: No. Putney: You made an o¡ the cu¡ remark when you were talking about the Drosophila TRPL, INAD and FKBP interactions, that you saw the same thing in S2 cells. Do S2 cells express TRPL? Schilling: We identi¢ed TRPL in S2 cell lysates by Western blot analysis. S2 cells also express FKBP and we were able to co-immunoprecipitate TRPL and FKBP59 from S2 cell lysates. Putney: What is the function of TRPL in S2 cells?