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Christian-Albrechts-Universität zu Kiel

Institut für Humanernährung und Lebensmittelkunde
Molekulare Prävention - Prof. Dr. Frank Döring

         
 

 

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The power of using abstraction is the essence of intellect, and with every increase in abstraction the intellectual triumphs of science are enhanced

(Bertrand Russel 1872-1971)

 

You have made your way from worm to man, but much in you is still a worm

(Friedrich Nietzsche 1844 - 1900)

 

 

 

Function of the potassium leak channel TWK-7 in adaptive locomotion behavior

 

The change of locomotion activity in response to external cues is a considerable achievement of animals and is required for escape responses, foraging, and other complex behaviors. We found that dietary restriction accelerates specifically the swimming gait. This response might represent a survival strategy, allowing food-deprived nematodes to exit unfavourable environments (Lüersen et al. 2014). The knowledge about the molecular regulators of such an adaptive locomotion behavior is rather limited. The conserved eukaryotic two-pore domain potassium channels (K2P) channels are recognized as voltage-independent background K+ channels that modify the membrane potential of cells. By using the Caenorhabditis elegans system combined with cell type specific approaches and locomotion analyses in-depth we found that the K2P channel TWK-7 affects the activity of two locomotory gaits, swimming and crawling, in a coordinated mode. TWK-7 is expressed in cholinergic excitatory B-type and GABAergic inhibitory D-type motor neurons to affect fundamental aspects of adaptive locomotion behavior which may be characteristic for a stimulus induced fast targeted movement (Lüersen et al. 2016)

In order to unravel signaling pathways that might act through TWK-7, we identified a loss-of function allele cau-1 of KIN-2 in a forward genetic screen. The gene kin-2 encodes the negative regulatory subunit of the C. elegans protein kinase A (PKA/KIN-1) which is part of the canonical Gαs pathway. An activated Gαs-PKA pathway and/or the absent of TWK-7 pores epistatically induced a persistent fast straightforward crawling behavior in GABAergic D-type motor neurons. Whereby, the five central aspects of stimulated locomotion - velocity, direction, wave parameters, duration and straightness - were synchronically affected by both the Gαs-PKA pathway and TWK-7. In conclusion, we found that TWK-7 acts in cholinergic B-type and GABAergic D-type motor neurons as a prime candidate for the modulation of locomotor activity and locomotion behavior that enables persistent fast and straightforward locomotion (Gottschling et al. 2017).

 

We presented convincing evidence for an epistatic interaction between the Gαs-PKA pathway and TWK-7 which most probably shares a common pathway being involved in the modulation of both locomotor activity and locomotion behavior during forward crawling that may mimic an adaptive response to specific environmental cues. Thus, we uncover a simple mechanism where a complex locomotion behavior might be modulated at the level of certain types of motor neurons by the activity of the Gαs-PKA pathway acting epistatically through the leak K+ channel TWK-7.

 

 

 

 

 

 

 

 

 

 

 

 
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