Phototransduction mechanisms in Drosophila microvillar photoreceptors

Abstract

Phototransduction in Drosophila is mediated by a G-protein coupled phospholipase C (PLC) cascade leading to graded membrane depolarization. It is the preferred model for phototransduction in microvillar photoreceptors and an important model for the ubiquitous phosphoinositide signaling cascade. The photoreceptors respond sensitively to single photons 10-100× more rapidly than vertebrate rods, yet still light adapt to signal under full sunlight. Incident light is absorbed and transduced in the rhabdomere, a 1-2 µm diameter, 100 µm long waveguide composed of ∼30,000 tightly packed microvilli, which contain the visual pigment rhodopsin and all the major components of the cascade. PLC hydrolyzes phosphatidyl-inositol (4,5) bisphosphate (PIP 2 ) to generate diacylglycerol (DAG), inositol (1,4,5) trisphosphate (InsP 3 ), and also a proton. This results in activation of two classes of Ca 2+ permeable cation channels, TRP and TRPL-the prototypical members of the transient receptor potential (TRP) superfamily of cation channels. Recent evidence suggests that the channels may be activated in a combinatorial manner by two neglected consequences of PLC activity, namely simultaneous depletion of PIP 2 and acidification. Several components of the cascade, including TRP, PLC, and protein kinase C are assembled into multimolecular signaling complexes by the PDZ-domain scaffolding protein INAD. Ca 2+ influx via TRP channels is essential for rapid kinetics, amplification, and light adaptation and mediates both positive and negative feedback via multiple downstream targets, including the channels, rhodopsin, and PLC. This Ca 2+ -dependent feedback along with the ultracompartmentalization provided by the microvillar design and molecular scaffolding is critical for the combination of sensitivity, rapid kinetics, and broad dynamic range. 

Shunt peaking in neural membranes

“…These neurons transmit the signals produced by the fastest known G-protein biochemical cascade [12], but their membrane capacitance is inflated by thousands of microvilli that capture and transduce photons. Reducing the number and size of these microvilli to decrease capacitance would, however, impair performance by reducing quantum catch and increasing noise [13,14].…”

Depletion of PtdIns(4,5)P2 underlies retinal degeneration in Drosophila trp mutants

“…The channels are present within ,30,000 tightly packed microvilli, forming a lightguiding 'rhabdomere', and are activated by a canonical G-proteincoupled signalling cascade involving rhodopsin (Rh1, encoded by ninaE), Gq protein (Gaq) and phospholipase C (PLC, encoded by norpA). PLC hydrolyses the membrane phospholipid, phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ], leading, by a still unresolved mechanism, to activation of the light-sensitive channels (Hardie, 2012;Katz and Minke, 2009;Montell, 2012). Drosophila TRP is highly Ca 2 selective and responsible for massive Ca 2+ influx during the response to light (Hardie, 1996;Hardie and Minke, 1992;Peretz et al, 1994b).…”

Bill Pak's Vision: The Neurogenetics of Phototransduction

“…Ching Kung gave a humorous perspective on the effort in a presentation in 2002 (see Figure 1). At least 20 of these genes have been subjected to extensive molecular characterization (Hardie, 2012;Montell, 2012;Pak, 2010). One result is that Drosophila is now the premier research organism for studies on invertebrate visual function.…”