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cAMP-Dependent Axon Guidance Is Distinctly Regulated by Epac and Protein Kinase A

Murray, Andrew J., Tucker, Steven J., Shewan, Derryck A.·2009·The Journal of Neuroscience
DOI 10.1523/jneurosci.3071-09.2009
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Abstract

cAMP is a key mediator of a number of molecules that induce growth cone chemotaxis, including netrin-1 and myelin-associated glycoprotein (MAG). Endogenous neuronal cAMP levels decline during development, and concomitantly axonal growth cones switch their response to cAMP-dependent guidance cues from attraction to repulsion. The mechanisms by which cAMP regulates these polarized growth cone responses are unknown. We report that embryonic growth cone attraction to gradients of cAMP, netrin-1, or MAG is mediated by Epac. Conversely, the repulsion conferred by MAG or netrin-1 on adult growth cones is mediated by protein kinase A (PKA). Furthermore, fluorescence resonance energy transfer reveals that netrin-1 distinctly activates Epac in embryonic growth cones but PKA in postnatal neurons. Our results suggest that cAMP mediates growth cone attraction or repulsion by distinctly activating Epac or PKA, respectively. Moreover, we propose that the developmental switch in growth cone response to gradients of cAMP-dependent guidance cues from attraction to repulsion is the result of a switch from Epac- to PKA-mediated signaling pathways.

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  • CAV1 enhances pro-survival and pro-growth signaling by concentrating neurotransmitter and neurotrophin receptors at membrane microdomains and/or lipid rafts, modulating pathways such as cAMP formation.

    “For instance, CAV1 enhances pro-survival and pro-growth signaling by concentrating neurotransmitter and neurotrophin receptors at membrane microdomains and/or lipid rafts, thus modulating signaling pathways such as the formation of cyclic adenosine monophosphate (cAMP), which has been shown to regulate the growth and guidance of developing axons (46).”

    From Hereditary spastic paraplegia SPG8 mutations impair CAV1-dependent, integrin-mediated cell adhesion (2020) · cites this paper as [46]

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Metadata

Authors
Murray, A. J., Tucker, S. J., & Shewan, D. A.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2009-12-09
Volume
29
Issue
49
Pages
15434-15444
ISSN
  • 0270-6474
  • 1529-2401
DOI
10.1523/jneurosci.3071-09.2009
Cited by
80
References
1
Language
en
Licence
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)

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