Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones
Year: 2006
Type: article
Abstract: Growth cones at the tips of nascent and regenerating axons direct axon elongation. Netrin-1, a secreted molecule that promotes axon outgrowth and regulates axon pathfinding, elevates cyclic AMP (cAMP) levels in growth cones and regulates growth cone morphology and axonal outgrowth. These morphological effects depend on the intracellular levels of cAMP. However, the specific pathways that regulate cAMP levels in response to netrin-1 signaling are unclear. Here we show that 'soluble' adenylyl cyclase (sAC), an atypical calcium-regulated cAMP-generating enzyme previously implicated in sperm maturation, is expressed in developing rat axons and generates cAMP in response to netrin-1. Overexpression of sAC results in axonal outgrowth and growth cone elaboration, whereas inhibition of sAC blocks netrin-1-induced axon outgrowth and growth cone elaboration. Taken together, these results indicate that netrin-1 signals through sAC-generated cAMP, and identify a fundamental role for sAC in axonal development.
Source: Nature Neuroscience
DOI: 10.1038/nn1767
Institutions: Cornell University, Weill Cornell Medicine
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Awards: SOLUBLE ADENYLYL CYCLASE ACTIVITY IN MALE GERM CELLS, G2582268275, G2882288742, G337788021, Bicarbonate regulated adenylyl cyclase, G6816120806, Cancer Pharmacology, Pharmacology and Neuroscience of Drug Abuse, G8183700289, Neuronal growth factor signaling via cAMP, Detection and characterization of nitric oxide effectors, Weill Cornell/Rockefeller/Sloan Kettering MST Program
OpenAlex ID: W2045539365