Exchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B
Author
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Muñoz Llancao, Pablo
Author
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Henríquez, Daniel R.
Author
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Wilson, Carlos
Author
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Bodaleo, Felipe
Author
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Boddeke, Erik W.
Author
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Lezoualc'h, Frank
Author
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Schmidt, Martina
Author
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González Billault, Christian
Admission date
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2015-12-03T00:48:21Z
Available date
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2015-12-03T00:48:21Z
Publication date
dc.date.issued
2015
Cita de ítem
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The Journal of Neuroscience, August 12, 2015 • 35(32):11315–11329
en_US
Identifier
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DOI: 10.1523/JNEUROSCI.3645-14.2015
Identifier
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https://repositorio.uchile.cl/handle/2250/135439
General note
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Artículo de publicación ISI
en_US
Abstract
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Acquisition of neuronal polarity is a complex process involving cellular and molecular events. The second messenger cAMP is involved in axonal specification through activation of protein kinase A. However, an alternative cAMP-dependent mechanism involves the exchange protein directly activated by cAMP (EPAC), which also responds to physiological changes in cAMP concentration, promoting activation of the small Rap GTPases. Here, we present evidence that EPAC signaling contributes to axon specification and elongation. In primary rat hippocampal neurons, EPAC isoforms were expressed differentially during axon specification. Furthermore, 8-pCPT, an EPAC pharmacological activator, and genetic manipulations of EPAC in neurons induced supernumerary axons indicative of Rap1b activation. Moreover, 8-pCPT-treated neurons expressed ankyrin G and other markers of mature axons such as synaptophysin and axonal accumulation of vGLUT1. In contrast, pharmacological inhibition of EPAC delayed neuronal polarity. Genetic manipulations to inactivate EPAC1 using either shRNA or neurons derived from EPAC1 knock-out (KO) mice led to axon elongation and polarization defects. Interestingly, multiaxonic neurons generated by 8-pCPT treatments in wild-type neurons were not found in EPAC1 KO mice neurons. Altogether, these results propose that EPAC signaling is an alternative and complementary mechanism for cAMP-dependent axon determination.
en_US
Patrocinador
dc.description.sponsorship
Fondecyt
3130316
1140325
Research Ring from CONICYT, Chile
ACT-1114