dc.creatorMuñoz Llancao, Pablo
dc.creatorHenríquez, Daniel R.
dc.creatorWilson, Carlos
dc.creatorBodaleo, Felipe
dc.creatorBoddeke, Erik W.
dc.creatorLezoualc'h, Frank
dc.creatorSchmidt, Martina
dc.creatorGonzález Billault, Christian
dc.date.accessioned2015-12-03T00:48:21Z
dc.date.available2015-12-03T00:48:21Z
dc.date.created2015-12-03T00:48:21Z
dc.date.issued2015
dc.identifierThe Journal of Neuroscience, August 12, 2015 • 35(32):11315–11329
dc.identifierDOI: 10.1523/JNEUROSCI.3645-14.2015
dc.identifierhttps://repositorio.uchile.cl/handle/2250/135439
dc.description.abstractAcquisition 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.
dc.languageen
dc.publisherSoc. Neuroscience
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.subjectAxon
dc.subjectAxon initial segment
dc.subjectCytoskeleton
dc.subjectEPAC signaling
dc.subjectNeuronal polarity
dc.subjectRap1b signaling
dc.titleExchange Protein Directly Activated by cAMP (EPAC) Regulates Neuronal Polarization through Rap1B
dc.typeArtículo de revista


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