Phosphoinositide-mediated phototransduction in Drosophila photoreceptors: the role of Ca2+ and trp

Abstract

Drosphoinate photoreceptors, represent a paradigm for the genetic dissection of phototransduction and, more generally for Ca2+ signaling. As in most invertebrates, phototransduction in Drosophila is mediated by the phosphoinositide (PI) cascade and is completely blocked by null mutations of the norpA gene which encodes a phospholipase C-beta isoform. The light-activated conductance in Drosophila is normally highly permeable to Ca2+, but in null mutants of the trp gene Ca2+ permeability is greatly reduced. Furthermore, the trp gene sequence shows homologies with voltage gated Ca2+ channels, suggesting that trp encodes a light-sensitive channel subunit. Ca2+ influx via these channels is instrumental in light adaptation, and profoundly influences phototransduction via positive and negative feedback at multiple molecular targets including protein kinase C. The mechanism of activation of the light-sensitive channels remains unresolved. A requirement for Ca2+ release from internal stores is suggested by the finding that Drosophila photoreceptors cannot sustain a maintained response under various conditions which might be expected to result in depletion of Ca2+ stores. However, Ca2+ release cannot be detected by Ca2+ indicator dyes and raising Ca2+ by photorelease of caged Ca2+ fails to mimic excitation. Recent studies, both in situ and with heterologously expressed trp protein, suggest that the trp-dependent channels may be activated by a process analogous to 'capacitative Ca2+ entry', a widespread, but poorly understood mode of PI-regulated Ca2+ influx in vertebrate cells.