Drosophila Photoreceptors and Signaling Mechanisms

Fly eyes have been a useful biological system in which fundamental principles of sensory signaling have been elucidated. The physiological optics of the fly compound eye, which was discovered in the Musca, Calliphora and Drosophila flies, has been widely exploited in pioneering genetic and developmental studies. The detailed photochemical cycle of bistable photopigments has been elucidated in Drosophila using the genetic approach. Studies of Drosophila phototransduction using the genetic approach have led to the discovery of novel proteins crucial to many biological processes. A notable example is the discovery of the inactivation no afterpotential D scaffold protein, which binds the light-activated channel, its activator the phospholipase C and it regulator protein kinase C. An additional protein discovered in the Drosophila eye is the light-activated channel transient receptor potential (TRP), the founding member of the diverse and widely spread TRP channel superfamily. The fly eye has thus played a major role in the molecular identification of processes and proteins with prime importance

Open Channel Block by Ca2+ Underlies the Voltage Dependence of Drosophila TRPL Channel

The light-activated channels of Drosophila photoreceptors transient receptor potential (TRP) and TRP-like (TRPL) show voltage-dependent conductance during illumination. Recent studies implied that mammalian members of the TRP family, which belong to the TRPV and TRPM subfamilies, are intrinsically voltage-gated channels. However, it is unclear whether the Drosophila TRPs, which belong to the TRPC subfamily, share the same voltage-dependent gating mechanism. Exploring the voltage dependence of Drosophila TRPL expressed in S2 cells, we found that the voltage dependence of this channel is not an intrinsic property since it became linear upon removal of divalent cations. We further found that Ca2+ blocked TRPL in a voltage-dependent manner by an open channel block mechanism, which determines the frequency of channel openings and constitutes the sole parameter that underlies its voltage dependence. Whole cell recordings from a Drosophila mutant expressing only TRPL indicated that Ca2+ block also accounts for the voltage dependence of the native TRPL channels. The open channel block by Ca2+ that we characterized is a useful mechanism to improve the signal to noise ratio of the response to intense light when virtually all the large conductance TRPL channels are blocked and only the low conductance TRP channels with lower Ca2+ affinity are active

Excess of Gβe over Gqαe in vivo prevents dark, spontaneous activity of Drosophila photoreceptors

Drosophila melanogaster photoreceptor cells are capable of detecting single photons. This utmost sensitivity is critically dependent on the maintenance of an exceedingly low, dark, spontaneous activity of photoreceptor cells. However, the underlying mechanisms of this hallmark of phototransduction are not fully understood. An analysis of the Drosophila visual heterotrimeric (αβγ) Gq protein revealed that wild-type Drosophila flies have about a twofold excess of Gβ over Gα subunits of the visual Gq protein. Studies of Gβe mutants in which the excess of Gβ was genetically eliminated showed dramatic dark, spontaneous activity of the photoreceptor cells, whereas concurrent genetic reduction of the Gα subunit, which restored the excess of Gβ, abolished this effect. These results indicate that an excess of Gβ over Gα is a strategy used in vivo for the suppression of spontaneous activity, thereby yielding a high signal to noise ratio, which is characteristic of the photoreceptor light response. This mechanism could be relevant to the regulation of G protein signaling in general

Light-regulated interaction of Dmoesin with TRP and TRPL channels is required for maintenance of photoreceptors

Recent studies in Drosophila melanogaster retina indicate that absorption of light causes the translocation of signaling molecules and actin from the photoreceptor's signaling membrane to the cytosol, but the underlying mechanisms are not fully understood. As ezrin-radixin-moesin (ERM) proteins are known to regulate actin–membrane interactions in a signal-dependent manner, we analyzed the role of Dmoesin, the unique D. melanogaster ERM, in response to light. We report that the illumination of dark-raised flies triggers the dissociation of Dmoesin from the light-sensitive transient receptor potential (TRP) and TRP-like channels, followed by the migration of Dmoesin from the membrane to the cytoplasm. Furthermore, we show that light-activated migration of Dmoesin results from the dephosphorylation of a conserved threonine in Dmoesin. The expression of a Dmoesin mutant form that impairs this phosphorylation inhibits Dmoesin movement and leads to light-induced retinal degeneration. Thus, our data strongly suggest that the light- and phosphorylation-dependent dynamic association of Dmoesin to membrane channels is involved in maintenance of the photoreceptor cells