Conserved modules required for Drosophila TRP function in vivo.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Zijing ChenCraig Montell

Abstract

TRP channels are broadly required in animals for sensory physiology. To provide insights into regulatory mechanisms, the structures of many TRPs have been solved. This has led to new models, some of which have been tested in vitro Here, using the classical TRP required for Drosophila visual transduction, we uncovered structural requirements for channel function in photoreceptor cells. Using a combination of molecular genetics, field recordings, protein expression analysis, and molecular modeling, we interrogated roles for the S4-S5 linker and the TRP domain, and revealed mutations in the S4-S5 linker that impair channel opening or closing. We also uncovered differential requirements for the two highly conserved motifs in the TRP domain for activation and protein stability. By performing genetic complementation, we found an intra-subunit interaction between the S4-S5 linker and the S5 segment that contributes to activation. This analysis highlights key structural requirements for TRP channel opening, closing, folding and for intra-subunit interactions in a native context-Drosophila photoreceptor cells.SIGNIFICANCE STATEMENT:The importance of TRP channels for sensory biology and human health has motivated tremendous effort in try...Continue Reading

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