Calcium Homeostasis in Fly Photoreceptor Cells

Abstract

In fly photoreceptor cells, two processes dominate the Ca²⁺ homeostasis: light-induced Ca²⁺ influx through members of the TRP family of ion channels, and Ca²⁺ extrusion by Na⁺/Ca²⁺ exchange. Ca²⁺ release from intracellular stores is quantitatively insignificant. Both, the light-activated channels and the Ca²⁺-extruding exchangers are located in or close to the rhabdomeric microvilli, small protrusions of the plasma membrane. The microvilli also contain the molecular machinery necessary for generating quantum bumps, short electrical responses caused by the absorption of a single photon. Due to this anatomical arrangement, the light-induced Ca²⁺ influx results in two separate Calf signals that have different functions: a global, homogeneous increase of the Ca²⁺ concentration in the cell body, and rapid but large amplitude Ca²⁺ transients in the microvilli. The global rise of the Ca²⁺ concentration mediates light adaptation, via regulatory actions on the phototransduction cascade, the voltage-gated K⁺ channels and small pigment granules controlling the light intensity. The local Ca²⁺ transients in the microvilli are responsible for shaping the quantum bumps into fast, all-or-nothing events. They achieve this by facilitating strongly the phototransduction cascade at early stages of the light response and subsequently inhibiting it. Many molecular targets of these feedback mechanisms have been identified and characterized due to the availability of numerous Drosophila mutant showing defects in the phototransduction. been identified that are regulated by Calf, either directly or by binding to Ca²⁺1 calmodulin or by Ca²⁺-dependent phosphorylation and dephosphorylations (Figure.12). In the overwhelming majority of cases, interfering with these mechanisms produces flies that have abnormally prolonged termination phases of the light response, i.e., show defects in the negative regulation of the phototransduction. The PKC INAC and the unconventional myosin NINAC have been proposed to additionally play a role in light adaptation, i.e., in the regulation of the sensitivity of the phototransduction cascade. Also, two candidates for positive Ca²⁺-dependent feedback have been identified, the channel-protein TRP and the PLC(3 NORPA. However, the more interesting, albeit much harder, question how these different regulatory events play together to produce their macroscopic effect on the physiology of the photoreceptor cells has not yet been tackled. An advance of our knowledge in this direction will probably demand a more quantitative understanding of the Ca²⁺-dependent processes and their consequences, as well as a detailed analysis of their time course, probably down to the millisecond range. This will allow to integrate the different pathways that have already been identified into a combined model of how Ca²⁺ brings about its regulation of fly phototransduction. The search for answers to these questions will no doubt increase not only our knowledge of fly phototransduction, but will also further our general understanding of how complex signaling cascades can be modulated and adapted to the prevailing environmental needs.