In vivo identification and manipulation of the Ca2+ selectivity filter in the Drosophila transient receptor potential channel

Che H. Liu, Tao Wang, Marten Postma, Alexander G. Obukhov, Craig Montell, Roger C. Hardie

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Null 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.

Original languageEnglish (US)
Pages (from-to)604-615
Number of pages12
JournalJournal of Neuroscience
Volume27
Issue number3
DOIs
StatePublished - Jan 17 2007

Keywords

  • Calcium channel
  • Permeability
  • Photoreceptor
  • Pore
  • Retinal degeneration
  • TRP channels
  • TRPC

ASJC Scopus subject areas

  • Neuroscience(all)

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