RRC ID 46225
Author Wang H, Sieburth D.
Title PKA controls calcium influx into motor neurons during a rhythmic behavior.
Journal PLoS Genet
Abstract Cyclic adenosine monophosphate (cAMP) has been implicated in the execution of diverse rhythmic behaviors, but how cAMP functions in neurons to generate behavioral outputs remains unclear. During the defecation motor program in C. elegans, a peptide released from the pacemaker (the intestine) rhythmically excites the GABAergic neurons that control enteric muscle contractions by activating a G protein-coupled receptor (GPCR) signaling pathway that is dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN-1, is the sole cAMP target in this pathway and that PKA is essential for enteric muscle contractions. Genetic analysis using cell-specific expression of dominant negative or constitutively active PKA transgenes reveals that knockdown of PKA activity in the GABAergic neurons blocks enteric muscle contractions, whereas constitutive PKA activation restores enteric muscle contractions to mutants defective in the peptidergic signaling pathway. Using real-time, in vivo calcium imaging, we find that PKA activity in the GABAergic neurons is essential for the generation of synaptic calcium transients that drive GABA release. In addition, constitutively active PKA increases the duration of calcium transients and causes ectopic calcium transients that can trigger out-of-phase enteric muscle contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our results suggest that PKA activates neurons during a rhythmic behavior by promoting presynaptic calcium influx through specific voltage-gated calcium channels.
Volume 9(9)
Pages e1003831
Published 2013
DOI 10.1371/journal.pgen.1003831
PMID 24086161
PMC PMC3784516
MeSH Animals Behavior, Animal / physiology Caenorhabditis elegans / genetics* Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / metabolism Calcium / metabolism* Calcium Channels / metabolism Calcium Signaling / genetics* Calcium Signaling / physiology Catalytic Domain / genetics Cyclic AMP / genetics Cyclic AMP / metabolism Cyclic AMP-Dependent Protein Kinases / genetics* Cyclic AMP-Dependent Protein Kinases / metabolism Defecation / genetics Defecation / physiology GABAergic Neurons / metabolism Membrane Proteins / metabolism Motor Neurons / metabolism* Muscle Contraction / genetics* Muscle Contraction / physiology Muscle Proteins / metabolism
IF 5.224
Times Cited 51
C.elegans tm4267 tm5036 tm4085 tm4267