Abstract
Increasing evidence indicates that the white (w) gene in Drosophila possesses extra-retinal functions in addition to its classical role in eye pigmentation. We have previously shown that w+ promotes fast and consistent locomotor recovery from anoxia, but how w+ modulates locomotor recovery is largely unknown. Here we show that in the absence of w+, several PDE mutants, especially cyclic guanosine monophosphate (cGMP)-specific PDE mutants, display wildtype-like fast locomotor recovery from anoxia, and that during the night time, locomotor recovery was light-sensitive in white-eyed mutant w1118, and light-insensitive in PDE mutants under w1118 background. Data indicate the involvement of cGMP in the modulation of recovery timing and presumably, light-evoked cGMP fluctuation is associated with light sensitivity of locomotor recovery. This was further supported by the observations that w-RNAi-induced delay of locomotor recovery was completely eliminated by upregulation of cGMP through multiple approaches, including PDE mutation, simultaneous overexpression of an atypical soluble guanylyl cyclase Gyc88E, or sildenafil feeding. Lastly, prolonged sildenafil feeding promoted fast locomotor recovery from anoxia in w1118. Taken together, these data suggest that a White-cGMP interaction modulates the timing of locomotor recovery from anoxia.
Highlights
The Drosophila white (w) gene encodes a hemi-unit of an ATP-binding cassette transporter (ABC transporter) which is proposed to transport a variety of small molecules including pigment precursors, 3-hydrokynurenine and bio-amines [1,2,3,4,5,6]
In Drosophila larvae, cyclic guanosine monophosphate mediates escape responses from hypoxia [20]. cGMP can be transported by White protein into vesicles in the principle cells of Malpighian tubules [21]. These findings suggest a hypothesis that a White—cGMP interaction could occur in adult flies and mediate locomotor responses to anoxia
We show that several PDE mutants, especially cGMP-specific PDE mutants, display wildtype-like fast locomotor recovery, and that locomotor recovery of w1118 was light-sensitive in the night, which was abolished in PDE mutants
Summary
The Drosophila white (w) gene encodes a hemi-unit of an ATP-binding cassette transporter (ABC transporter) which is proposed to transport a variety of small molecules including pigment precursors, 3-hydrokynurenine and bio-amines [1,2,3,4,5,6]. In addition to its classical role in eye pigmentation [7,8,9], increasing evidence indicates that the w gene has extra-retinal functions in the central nervous system (CNS) [4, 10,11,12]. We have recently shown that w+ is associated with fast and consistent locomotor recovery from anoxia in adult flies [13]. It is possible that the White protein possesses a housekeeping function in promoting appropriately timed release of second messengers or neurotransmitters and improving signaling efficacy during anoxic recovery. Little is PLOS ONE | DOI:10.1371/journal.pone.0168361 January 6, 2017
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