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Science 327 (5965): 547-552

Copyright © 2010 by the American Association for the Advancement of Science

Local and Long-Range Reciprocal Regulation of cAMP and cGMP in Axon/Dendrite Formation

Maya Shelly,1,* Byung Kook Lim,1,* Laura Cancedda,1,2 Sarah C. Heilshorn,1,{dagger} Hongfeng Gao,1 Mu-ming Poo1,{ddagger}

Abstract: Cytosolic cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) often mediate antagonistic cellular actions of extracellular factors, from the regulation of ion channels to cell volume control and axon guidance. We found that localized cAMP and cGMP activities in undifferentiated neurites of cultured hippocampal neurons promote and suppress axon formation, respectively, and exert opposite effects on dendrite formation. Fluorescence resonance energy transfer imaging showed that alterations of the amount of cAMP resulted in opposite changes in the amount of cGMP, and vice versa, through the activation of specific phosphodiesterases and protein kinases. Local elevation of cAMP in one neurite resulted in cAMP reduction in all other neurites of the same neuron. Thus, local and long-range reciprocal regulation of cAMP and cGMP together ensures coordinated development of one axon and multiple dendrites.

1 Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
2 Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genoa 16163, Italy.

* These authors contributed equally to this work.

{dagger}Present address: Department of Materials Science and Engineering, Geballe Laboratory for Advanced Materials, Stanford University, Stanford, CA 94305, USA.

{ddagger}To whom correspondence should be addressed. E-mail: mpoo{at}uclink.berkeley.edu


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