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

• Published in: Science (American Association for the Advancement of Science) Vol. 327; no. 5965; pp. 547 - 552
• Main Authors: Shelly, Maya, Lim, Byung Kook, Cancedda, Laura, Heilshorn, Sarah C, Gao, Hongfeng, Poo, Mu-ming
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 29.01.2010; The American Association for the Advancement of Science
• Subjects: Adenylyl Cyclase Inhibitors; Adenylyl Cyclases - metabolism; Animals; Axons; Axons - metabolism; Axons - physiology; Biochemistry; Biological and medical sciences; Cell culture techniques; Cell Differentiation; Cell Line; Cell Polarity; Cells, Cultured; Cellular biology; Cultured cells; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic GMP - metabolism; Dendrites; Dendrites - metabolism; Dendrites - physiology; Enzyme Inhibitors - pharmacology; Fluorescence; Fluorescence Resonance Energy Transfer; Fundamental and applied biological sciences. Psychology; Guanylate Cyclase - antagonists & inhibitors; Guanylate Cyclase - metabolism; Hippocampus - cytology; Humans; Kinases; Neurites; Neurites - metabolism; Neurites - physiology; Neurons; Neurons - cytology; Neurons - physiology; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - metabolism; Phosphorylation; Rats; Research Article; Signal Transduction; Small interfering RNA; Stripes; Transfection; Vertebrates: nervous system and sense organs; Neurite; Central nervous system; Cyclic AMP; Axon; 3',5'-GMP; Ionic channel; Extracellular; In vitro; Protein; Encephalon; Dendrite; Imaging; Cell volume; Hippocampus
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1179735

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.