Natural Variation in the Thermotolerance of Neural Function and Behavior due to a cGMP-Dependent Protein Kinase

Björn Brembs,Ken Dawson-Scully,Clement Kent,Gary A B Armstrong,Marla B Sokolowski,R Meldrum Robertson

doi:10.1371/journal.pone.0000773

Björn Brembs, Ken Dawson-Scully + Show 4 more

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https://doi.org/10.1371/journal.pone.0000773

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Journal: PloS one	Publication Date: Aug 22, 2007
Citations: 88	License type: CC BY 4.0

Affiliation: University of Toronto, Queen's University

Abstract

Although it is acknowledged that genetic variation contributes to individual differences in thermotolerance, the specific genes and pathways involved and how they are modulated by the environment remain poorly understood. We link natural variation in the thermotolerance of neural function and behavior in Drosophila melanogaster to the foraging gene (for, which encodes a cGMP-dependent protein kinase (PKG)) as well as to its downstream target, protein phosphatase 2A (PP2A). Genetic and pharmacological manipulations revealed that reduced PKG (or PP2A) activity caused increased thermotolerance of synaptic transmission at the larval neuromuscular junction. Like synaptic transmission, feeding movements were preserved at higher temperatures in larvae with lower PKG levels. In a comparative assay, pharmacological manipulations altering thermotolerance in a central circuit of Locusta migratoria demonstrated conservation of this neuroprotective pathway. In this circuit, either the inhibition of PKG or PP2A induced robust thermotolerance of neural function. We suggest that PKG and therefore the polymorphism associated with the allelic variation in for may provide populations with natural variation in heat stress tolerance. for's function in behavior is conserved across most organisms, including ants, bees, nematodes, and mammals. PKG's role in thermotolerance may also apply to these and other species. Natural variation in thermotolerance arising from genes involved in the PKG pathway could impact the evolution of thermotolerance in natural populations.

Highlights

Exposure to extreme ambient temperatures will result in the eventual failure of normal neural functioning
At extremely high but sub-lethal temperatures, neural failure occurs through a string of events that start with motor pattern arrhythmicity which leads to spreading depression and eventual synaptic transmission failure
We found that the phosphatase 2A (PP2A)-specific inhibitor Cantharidin increased the thermotolerance of synaptic transmission as strongly as did the PKG inhibitor (Figure 1B)

Summary

Introduction

Exposure to extreme ambient temperatures will result in the eventual failure of normal neural functioning. In locusts, similar transient and reduced K+ currents have been associated with heat shock-mediated protection of neural function, including induced thermotolerance of synaptic transmission [14] and central pattern generation [4]. Fors2, the sitter mutant generated on a rover genetic background exhibited significantly higher failure temperatures than fors and forR suggesting that sitters with their lower PKG levels have increased thermotolerance [11].

Results

Conclusion