Requirement for the PDZ domain protein, INAD, for localization of the TRP store-operated channel to a signaling complex.
In Drosophila, the store-operated Ca2+ channel, TRP, is required in photoreceptor cells for a sustained response to light. Here, we show that TRP forms a complex with phospholipase C-beta (NORPA), rhodopsin (RH1), calmodulin, and the PDZ domain containing protein INAD. Proteins with PDZ domains have previously been shown to cluster ion channels in vitro. We show that in InaD mutant flies, TRP is no longer spatially restricted to its normal subcellular compartment, the rhabdomere. These results provide evidence that a PDZ domain protein is required, in vivo, for anchoring of an ion channel to a signaling complex. Furthermore, disruption of this interaction results in retinal degeneration. We propose that the TRP channel is linked to NORPA and RH1 to facilitate feedback regulation of these upstream signaling molecules.
Chevesich
J
J
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kreuz
A J
AJ
Montell
C
C
D000595:Amino Acid Sequence; D000818:Animals; D015220:Calcium Channels / Q000096:biosynthesis / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology; D005136:Eye Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D005246:Feedback; D017344:Genes, Insect; D008961:Models, Structural; D009154:Mutation; D010786:Photoreceptor Cells / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D050052:TRPC Cation Channels
D015220:Calcium Channels; D002147:Calmodulin; D029721:Drosophila Proteins; D005136:Eye Proteins; D011993:Recombinant Fusion Proteins; D050052:TRPC Cation Channels; C091568:inaD protein, Drosophila; C096351:transient receptor potential cation channel, subfamily C, member 1