TRP cation channels are conserved throughout animal phylogeny and include many members that function in sensory physiology. The founding TRP is required for Drosophila photo-transduction and has served as a paradigm for unravelling the roles and macromolecular organizations of TRP channels in native tissues. Two other TRPC channels, TRPL and TRP-γ, are expressed in photoreceptor cells and form heteromultimers with TRP and with each other. TRP is a member of a supramolecular signalling complex, the signalplex, which includes the PDZ scaffold protein, INAD, and two other core members that remain bound and depend on INAD for localization. Other INAD binding proteins are proposed to interact dynamically with INAD, one of which, TRPL, undergoes light-dependent translocation in photoreceptor cells. Surprisingly, TRP has non-channel functions, including an anchoring role necessary for retaining INAD in the rhabdomeres. Loss of TRP function or constitutive TRP activity results in retinal degeneration, which can be suppressed by disruption or overexpression of the Na+/Ca2+ exchanger, CalX, respectively. Given that hypoxia-induced constitutive activity of some mammalian TRPs leads to neuronal cell death, interventions that increase Na+/Ca2+ exchanger or decrease TRP function have the potential to reduce the severity of cell death due to ischaemia.
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