Locomotion Behavior Is Affected by the GαSPathway and the Two-Pore-Domain K+Channel TWK-7 Interacting in GABAergic Motor Neurons inCaenorhabditis elegans.
Adjusting the efficiency of movement in response to environmental cues is an essential integrative characteristic of adaptive locomotion behavior across species. However, the modulatory molecules and the pathways involved are largely unknown. Recently, we demonstrated that inCaenorhabditis elegans, a loss-of-function of the two-pore-domain potassium (K2P) channel TWK-7 causes a fast, coordinated, and persistent forward crawling behavior in which five central aspects of stimulated locomotion-velocity, direction, wave parameters, duration, and straightness-are affected. Here, we isolated the reduction-of-function allelecau1of theC. elegansgenekin-2in a forward genetic screen and showed that it phenocopies the locomotor activity and locomotion behavior oftwk-7(null)animals.Kin-2encodes the negative regulatory subunit of protein kinase A (KIN-1/PKA). Consistently, we found that other gain-of-function mutants of the GαS-KIN-1/PKA pathway resemblekin-2(cau1)andtwk-7(null)in locomotion phenotype. Using the powerful genetics of theC. eleganssystem in combination with cell type-specific approaches and detailed locomotion analyses, we identified TWK-7 as a putative downstream target of the GαS-KIN-1/PKA pathway at the level of the γ-aminobutyric acid (GABA)ergic D-type motor neurons. Due to this epistatic interaction, we suggest that KIN-1/PKA and TWK-7 may share a common pathway that is probably involved in the modulation of both locomotor activity and locomotion behavior during forward crawling.
Department of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, 24118, Germany.
Dieter-Christian
DC
Gottschling
Department of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, 24118, Germany.
Frank
F
Döring
Department of Molecular Prevention, Institute of Human Nutrition and Food Science, Christian-Albrechts-University of Kiel, 24118, Germany luersen@foodsci.uni.kiel.de.
Kai
K
Lüersen
D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D059330:GABAergic Neurons / Q000378:metabolism / Q000502:physiology; D008124:Locomotion / Q000235:genetics*; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D015221:Potassium Channels; C000619213:TWK-7 protein, C elegans; D005680:gamma-Aminobutyric Acid; D017868:Cyclic AMP-Dependent Protein Kinases
C. elegans; PKA; locomotion; motor neurons; two-pore-domain potassium channel