New perspectives in cyclic AMP-mediated axon growth and guidance: The emerging epoch of Epac.
In the search for a cure to brain and spinal cord injury much has been learned about the inhibitory environment of the central nervous system (CNS), and yet a clinical therapy remains elusive. In recent years great advances have been made in understanding intracellular molecular mechanisms that transduce cell surface receptor-mediated signals that neurons receive from their environment. Many of these signalling pathways share common mechanisms, which presents the possibility that manipulating activities of key cell signalling molecules such as those regulated by 3'-5'-cyclic adenosine monophosphate (cAMP) might allow axons to simultaneously overcome the inhibitory effects of a number of extracellular ligands. The identification of Epac, a novel direct intracellular target for cAMP, has opened up a new avenue of research that is beginning to explain how cAMP can mediate a range of neuronal functions including distinct axon growth and guidance decisions. With current research tools that allow more specific activation of proteins or knock-down of their expression, as well as quantitation of protein activities in live cells, it is already becoming clear that Epac plays highly important roles in the development and function of the nervous system. Here, we focus on emerging evidence that Epac mediates cAMP-regulated axon growth and chemoattraction, and thus represents a novel target for overcoming axon growth inhibition and promoting CNS regeneration.
Peace
Andrew G
AG
Institute of Medical Sciences, School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Foresterhill, United Kingdom. A.Peace@abdn.ac.uk
Shewan
Derryck A
DA
D000818:Animals; D001369:Axons / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D054815:Cyclic Nucleotide-Gated Cation Channels; D020662:Guanine Nucleotide Exchange Factors; C526973:Rapgef3 protein, rat; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases