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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,
Hongfeng Gao,1
Mu-ming Poo1,
Abstract:
Cytosolic cyclic adenosine monophosphate (cAMP) and cyclic guanosinemonophosphate (cGMP) often mediate antagonistic cellular actionsof extracellular factors, from the regulation of ion channelsto cell volume control and axon guidance. We found that localizedcAMP and cGMP activities in undifferentiated neurites of culturedhippocampal neurons promote and suppress axon formation, respectively,and exert opposite effects on dendrite formation. Fluorescenceresonance energy transfer imaging showed that alterations ofthe amount of cAMP resulted in opposite changes in the amountof cGMP, and vice versa, through the activation of specificphosphodiesterases and protein kinases. Local elevation of cAMPin one neurite resulted in cAMP reduction in all other neuritesof the same neuron. Thus, local and long-range reciprocal regulationof cAMP and cGMP together ensures coordinated development ofone 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.
Present address: Department of Materials Science and Engineering,Geballe Laboratory for Advanced Materials, Stanford University,Stanford, CA 94305, USA.
To whom correspondence should be addressed. E-mail: mpoo{at}uclink.berkeley.edu
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Present address: Department of Materials Science and Engineering, Geballe Laboratory for Advanced Materials, Stanford University, Stanford, CA 94305, USA. 
To whom correspondence should be addressed. E-mail: 
