INAF, a protein required for transient receptor potential Ca2+ channel function

The trp gene of Drosophila encodes a subunit of a class of Ca2+-selective l ight-activated channels that carry the bulk of the phototransduction curren t. Transient receptor potential (TRP) homologs have been identified through out animal phylogeny. In vertebrates, TRP-related channels have been sugges ted to mediate "store-operated Ca2+ entry," which is important in Ca2+ home ostasis in a wide variety of cell types. However, the mechanisms of activat ion and regulation of the TRP channel are not known. Here, we report on the Drosophila inaF gene, which encodes a highly eye-enriched protein, INAF, t hat appears to be required for TRP channel function. A null mutation in thi s gene significantly reduces the amount of the TRP protein and, in addition , specifically affects the TRP channel function so as to nearly shut down i ts activity. The inaF mutation also dramatically suppresses the severe dege neration caused by a constitutively active mutation in the trp gene. Althou gh the reduction in the amount of the TRP protein may contribute to these p henotypes. several lines of evidence support the view that inaF mutations a lso more directly affect the TRP channel function, suggesting that the INAF protein may have a regulatory role in the channel function.