Mammalian TRP Channels as Molecular Targets - Novartis

This publication brings jointly contributions from key investigators within the region of temporary Receptor power (TRP) channel constitution and function.  It covers the constitution, functionality and legislation of mammalian TRP channels and mechanisms of sign transduction.  The discussions point out learn that will enhance figuring out of the function of TRP channels in general mobile body structure, the involvement of TRP channels in illness states and their power use as molecular pursuits for novel healing brokers

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NHERF has only two PDZ domains, yet it is supposed to be associated with everything ever known to be able to transport something. One has to be a little bit careful. I don’t know any activity that is associated with binding to PDZ domains that in one way or another hasn’t been shown to be a¡ected by binding to NHERF. Zhu: The same thing could be said for INAD. It doesn’t have an obvious e¡ect except for a small e¡ect on inactivation. We have to be careful not to try to deduce what the PDZ domain is doing from the limited amount of data.

Penner: Which endogenous, native system would people choose to look at TRPC1 with? If I were to identify a large response in a native system, where would I look for TRPC1? Zhu: Hippocampal pyramidal cells would be a good one. This is where you see the highest in situ signal. Schilling: That’s what I would say, also: neurons. But the channels might be TRPC1 and 4 or 5 heteromultimers. Zhu: TRPC1, 4 and 5 are all very high in hippocampal neurons. 42 DISCUSSION Authi: In terms of mRNA expression, I think smooth muscle cells have TRPC1 in reasonable amounts.

We need to perform sequential immunoprecipitation experiments to determine the native subunit composition of the individual channels in the brain. Penner: Have you tried TRPC1 overexpression in mammalian cells? It doesn’t work for us. Schilling: No. Perhaps it needs TRPC4 to help co-localize it to the plasma membrane as shown by Hofmann et al (2002). Have you tried that? Penner: No. Authi: We have been looking at platelets. We have detected a very small amount of TRPC1 that we can only see after immunoprecipitation, and we don’t see any TRPC4 or TRPC5 at all in the cell.

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