Coiled coils direct assembly of a cold-activated TRP channel.
Transient receptor potential (TRP) channels mediate numerous sensory transduction processes and are thought to function as tetramers. TRP channel physiology is well studied; however, comparatively little is understood regarding TRP channel assembly. Here, we identify an autonomously folded assembly domain from the cold- and menthol-gated channel TRPM8. We show that the TRPM8 cytoplasmic C-terminal domain contains a coiled coil that is necessary for channel assembly and sufficient for tetramer formation. Cell biological experiments indicate that coiled-coil formation is required for proper channel maturation and trafficking and that the coiled-coil domain alone can act as a dominant-negative inhibitor of functional channel expression. Our data define an authentic TRP modular assembly domain, establish a clear role for coiled coils in ion channel assembly, demonstrate that coiled-coil assembly domains are a general feature of TRPM channels, and delineate a new tool that should be of general use in dissecting TRPM channel function.
Tsuruda
Pamela R
PR
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California 94158, USA.
Julius
David
D
Minor
Daniel L
DL
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003080:Cold Temperature; D017124:Conserved Sequence; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D050053:TRPM Cation Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014981:Xenopus
D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat