RRC ID 30494
Author Wang H, Girskis K, Janssen T, Chan JP, Dasgupta K, Knowles JA, Schoofs L, Sieburth D.
Title Neuropeptide secreted from a pacemaker activates neurons to control a rhythmic behavior.
Journal Curr Biol
Abstract BACKGROUND:Rhythmic behaviors are driven by endogenous biological clocks in pacemakers, which must reliably transmit timing information to target tissues that execute rhythmic outputs. During the defecation motor program in C. elegans, calcium oscillations in the pacemaker (intestine), which occur about every 50 s, trigger rhythmic enteric muscle contractions through downstream GABAergic neurons that innervate enteric muscles. However, the identity of the timing signal released by the pacemaker and the mechanism underlying the delivery of timing information to the GABAergic neurons are unknown.
RESULTS:Here, we show that a neuropeptide-like protein (NLP-40) released by the pacemaker triggers a single rapid calcium transient in the GABAergic neurons during each defecation cycle. We find that mutants lacking nlp-40 have normal pacemaker function, but lack enteric muscle contractions. NLP-40 undergoes calcium-dependent release that is mediated by the calcium sensor, SNT-2/synaptotagmin. We identify AEX-2, the G-protein-coupled receptor on the GABAergic neurons, as the receptor for NLP-40. Functional calcium imaging reveals that NLP-40 and AEX-2/GPCR are both necessary for rhythmic activation of these neurons. Furthermore, acute application of synthetic NLP-40-derived peptide depolarizes the GABAergic neurons in vivo.
CONCLUSIONS:Our results show that NLP-40 carries the timing information from the pacemaker via calcium-dependent release and delivers it to the GABAergic neurons by instructing their activation. Thus, we propose that rhythmic release of neuropeptides can deliver temporal information from pacemakers to downstream neurons to execute rhythmic behaviors.
Volume 23(9)
Pages 746-54
Published 2013-5-6
DOI 10.1016/j.cub.2013.03.049
PII S0960-9822(13)00351-5
PMID 23583549
PMC PMC3651789
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Calcium / metabolism Calcium Signaling Defecation Intestines / physiology Molecular Sequence Data Muscle Contraction Neuropeptides / genetics Neuropeptides / metabolism* Receptors, G-Protein-Coupled / metabolism Sequence Alignment Sequence Analysis, DNA Synaptotagmin II / genetics Synaptotagmin II / metabolism
IF 9.601
Times Cited 21
C.elegans tm4085 tm1711