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Synaptogenesis regulates axotomy-induced activation of c-Jun-activator protein-1 transcription.


ABSTRACT: The activator protein-1 (AP1) transcription complex remains active for long periods after axotomy, but its activity diminishes during target contact. This raises the possibility that the function of this complex is regulated by the synaptic connections. Using Aplysia californica, we found that crushing peripheral nerves in vivo enhanced AP1 binding in the sensory neurons that lasted for weeks and then declined as regeneration was completed. The AP1 complex in Aplysia is a c-Jun homodimer. Its activation, after axotomy, is mediated by Aplysia c-Jun-N-terminal kinase (apJNK), which enters the nucleus of sensory neurons and phosphorylates c-Jun at Ser-73 (p73-c-Jun). Active AP1 in the sensory neurons did not mediate apoptosis and was not involved in the appearance of the long-term hyperexcitability that develops in these cells after axotomy, and blocking the activation of apJNK in vitro did not influence neurite outgrowth. In contrast, the levels of activated apJNK and p73-c-Jun declined markedly when sensory neurons formed synapses with motor neuron L7 in vitro. Furthermore, inhibiting the pathway accelerated synaptogenesis between sensory neurons and L7. These data suggest that positive and negative modulation of the JNK-c-Jun-AP1 pathway functions in alerting the nucleus to the loss and gain of synapses, respectively.

SUBMITTER: Sung YJ 

PROVIDER: S-EPMC6674025 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature

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Synaptogenesis regulates axotomy-induced activation of c-Jun-activator protein-1 transcription.

Sung Ying-Ju YJ   Wu Fang F   Schacher Samuel S   Ambron Richard T RT  

The Journal of neuroscience : the official journal of the Society for Neuroscience 20060601 24


The activator protein-1 (AP1) transcription complex remains active for long periods after axotomy, but its activity diminishes during target contact. This raises the possibility that the function of this complex is regulated by the synaptic connections. Using Aplysia californica, we found that crushing peripheral nerves in vivo enhanced AP1 binding in the sensory neurons that lasted for weeks and then declined as regeneration was completed. The AP1 complex in Aplysia is a c-Jun homodimer. Its ac  ...[more]

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