TRP Is Cracked but Is CRAC TRP?

fly's compound eye. Unlike many genetically identified proteins in this system, which are enzymes in the phos-Mayo Foundation Rochester, Minnesota 55905 phatidylinositol pathway, TRP and TRPL were originally presumed to be ion channels based on their putative It takes only one close look at a housefly to tell you six transmembrane-spanning topology and the phenotype of the associated trp mutants. TRP-deficient flies something is fundamentally different about insect vision. Besides being divided into numerous faceted compart-are blinded by intense light because their characteristic transient receptor potential fails to provide sustained ments, the fly's eye converts impinging photons into electrical signals destined for the brain in a very different Ca 2ϩ entry and subsequent Ca 2ϩ-dependent adaptation. It is just this role in sustaining Ca 2ϩ entry that piques way than do our eyes. In fact, most invertebrates appear to use one signal transduction mechanism and all verte-the interest of scientists outside the fly vision world. James Putney (1977) proposed that emptied calcium brates quite another. Four recent papers from Cell Press wrestle with the function of the Drosophila melanogaster stores somehow gate Ca 2ϩ entry in order to replenish the deficit (capacitative Ca 2ϩ entry). Although initially (fruit fly) eye-specific trp gene, its associated molecules, and the role for its six mammalian homologs more widely thought to occur via a preferred pathway directly into stores, repletion Ca 2ϩ more likely first enters the cyto-distributed outside the visual system (Niemeyer et al. Zitt et al., plasm from which smooth endoplasmic reticulum Ca 2ϩ transporters pump it into the ER. The physiological hall-1996 [this issue of Neuron]). The conclusions clarify fly vision, but the roles of the human homologs are still in mark of the capacitative Ca 2ϩ entry process is a large receptor-mediated transient [Ca 2ϩ ] i increase followed by the early stages of investigation. In the human retina (Figure 1), light impinges on a a prolonged high [Ca 2ϩ ] i plateau dependent on [Ca 2ϩ ] o. small, photosensitive molecule, retinal, nestled in the opsin receptor. The resulting activated receptor in turn and Penner, 1992) subsequently identified a very specific and highly Ca 2ϩ-selective current (Ca 2ϩ release– activates its associated G protein whose target, cGMP phosphodiesterase, then degrades cGMP. In the dark, activated current; I CRAC) initiated by a variety of store depletion protocols in whole-cell recordings from single the cGMP levels are high, and a steady …