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

Promoting Axon Formation How do neurons initiate one axon and lots of dendrites? Using an in vitro assay involving stripes of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), Shelly et al. (p. 547 ) show that an increase in cAMP initiates axon formation while an increase in cGMP initiates dendrites. Moreover, cAMP and cGMP reciprocally inhibit each other via the activation of specific phosphodiesterases, as well as protein kinase A and protein kinase G. Finally, long-range self-inhibition of cAMP can explain why only one axon, yet multiple dendrites, is initiated in single hippocampal neurons in culture. Locally increasing cAMP in one neurite causes long-range cAMP reduction in the rest of the neurites, accompanied by corresponding reciprocal changes in cGMP.