Liu, Che H.Wang, TaoPostma, MartenObukhov, Alexander G.Montell, CraigHardie, Roger C.2019-10-172019-10-172007-01-17Liu, C. H., Wang, T., Postma, M., Obukhov, A. G., Montell, C., & Hardie, R. C. (2007). In vivo identification and manipulation of the Ca2+ selectivity filter in the Drosophila transient receptor potential channel. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(3), 604–615. doi:10.1523/JNEUROSCI.4099-06.2007https://hdl.handle.net/1805/21183Null mutations in the transient receptor potential (trp) gene eliminate the major, Ca2+-selective component of the light-sensitive conductance in Drosophila photoreceptors. Although it is the prototypical member of the TRP ion channel superfamily, conclusive evidence that TRP is a pore-forming channel subunit in vivo is lacking. We show here that mutating a specific acidic residue (Asp621) in the putative pore virtually eliminated Ca2+ permeation in vivo and altered other biophysical properties of the native TRP conductance. The results identify Asp621 as a critical residue of the TRP Ca2+ selectivity filter, provide the first rigorous demonstration that a TRP protein is a pore-forming subunit in any native system, and point to the likely location of the pore in mammalian canonical TRP channels. The specific elimination of Ca2+ permeation in TRP also provided a unique opportunity to address the roles of Ca2+ influx in vivo. We found that Asp621 mutations profoundly affected several key aspects of the light response and caused light-dependent retinal degeneration.en-USPublisher PolicyPhotoreceptorPoreCalcium channelPermeabilityRetinal degenerationTRP channelsTRPCArticle