Drosophila TRP channels require a protein with a distinctive motif encoded by the inaF locus.
In both vertebrates and invertebrates, ion channels of the TRP superfamily are known to be influenced by a variety of accessory factors, but the list of interacting proteins is acknowledged to be incomplete. Although previous work showed that Drosophila TRP function is disrupted by mutations in the inaF locus, the mechanism of this effect has remained obscure. Here we show that a previously overlooked small protein, INAF-B, is encoded by the locus and fulfills its critical role in retinal physiology. The 81-aa INAF-B gene product is an integral membrane protein that colocalizes to rhabdomeres along with TRP channels. Immunoprecipitation experiments demonstrate that the two proteins participate in a complex, and blotting experiments show that neither protein survives in the absence of the other. Both proteins are normally part of a large supramolecular assembly, the signalplex, but their interaction persists even in the absence of the scaffold for this structure. The inaF locus encodes three other proteins, each of which has diverged from INAF-B except for a 32-aa block of residues that encompasses a transmembrane domain. This conserved sequence defines an inaF motif, representatives of which are found in proteins from organisms as diverse as nematodes, fish, and humans. Given the role of INAF-B, these proteins are good candidates for interacting partners of other members of the TRP superfamily.
Cheng
Yuzhong
Y
Laboratory of Molecular Biology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Nash
Howard A
HA
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D016678:Genome; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010641:Phenotype; D010786:Photoreceptor Cells / Q000502:physiology; D017384:Sequence Deletion; D050052:TRPC Cation Channels / Q000235:genetics*; D014158:Transcription, Genetic
D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D005136:Eye Proteins; D050052:TRPC Cation Channels; C400761:inaF protein, Drosophila