The balance between cytoplasmic and nuclear CaM kinase-1 signaling controls the operating range of noxious heat avoidance.
Neuron
; 84(5): 983-96, 2014 Dec 03.
Article
em En
| MEDLINE
| ID: mdl-25467982
ABSTRACT
Through encounters with predators, competitors, and noxious stimuli, animals have evolved defensive responses that minimize injury and are essential for survival. Physiological adaptation modulates the stimulus intensities that trigger such nocifensive behaviors, but the molecular networks that define their operating range are largely unknown. Here, we identify a gain-of-function allele of the cmk-1 CaMKI gene in C. elegans and show that loss of the regulatory domain of the CaMKI enzyme produces thermal analgesia and shifts the operating range for nocifensive heat avoidance to higher temperatures. Such analgesia depends on nuclear CMK-1 signaling, while cytoplasmic CMK-1 signaling lowers the threshold for thermal avoidance. CMK-1 acts downstream of heat detection in thermal receptor neurons and controls neuropeptide release. Our results establish CaMKI as a key regulator of the operating range for nocifensive behaviors and suggest strategies for producing thermal analgesia through the regulation of CaMKI-dependent signaling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Reação de Fuga
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Proteína Quinase Tipo 1 Dependente de Cálcio-Calmodulina
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Nociceptividade
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Temperatura Alta
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
Neuron
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Suíça