Common mechanisms regulating dark noise and quantum bump amplification in Drosophila photoreceptors.
Absolute visual thresholds are limited by "dark noise," which in Drosophila photoreceptors is dominated by brief (∼10 ms), small (∼2 pA) inward current events, occurring at ∼2/s, believed to reflect spontaneous G protein activations. These dark events were increased in rate and amplitude by a point mutation in myosin III (NINAC), which disrupts its interaction with the scaffolding protein, INAD. This phenotype mimics that previously described in null mutants of ninaC (no inactivation no afterpotential; encoding myosin III) and an associated protein, retinophilin (rtp). Dark noise was similarly increased in heterozygote mutants of diacylglycerol kinase (rdgA/+). Dark noise in ninaC, rtp, and rdgA/+ mutants was greatly suppressed by mutations of the Gq α-subunit (Gαq) and the major light-sensitive channel (trp) but not rhodopsin. ninaC, rtp, and rdgA/+ mutations also all facilitated residual light responses in Gαq and PLC hypomorphs. Raising cytosolic Ca(2+) in the submicromolar range increased dark noise, facilitated activation of transient receptor potential (TRP) channels by exogenous agonist, and again facilitated light responses in Gαq hypomorphs. Our results indicate that RTP, NINAC, INAD, and diacylglycerol kinase, together with a Ca(2+)-dependent threshold, share common roles in suppressing dark noise and regulating quantum bump generation; consequently, most spontaneous G protein activations fail to generate dark events under normal conditions. By contrast, quantum bump generation is reliable but delayed until sufficient G proteins and PLC are activated to overcome threshold, thereby ensuring generation of full-size bumps with high quantum efficiency.
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Brian
B
Chu
Che-Hsiung
CH
Liu
Sukanya
S
Sengupta
Amit
A
Gupta
Padinjat
P
Raghu
Roger C
RC
Hardie
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000502:physiology*; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism; D012684:Sensory Thresholds; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism
D029721:Drosophila Proteins; D005136:Eye Proteins; D050051:Transient Receptor Potential Channels; C520357:rtp protein, Drosophila; D012243:Rhodopsin; D019852:Diacylglycerol Kinase; C511350:RdgA protein, Drosophila; C072308:ninaC protein, Drosophila; D018995:Myosin Heavy Chains; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D002118:Calcium