Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones Academic Article uri icon


MeSH Major

  • Adenylyl Cyclases
  • Growth Cones
  • Nerve Growth Factors
  • Neurons, Afferent
  • Signal Transduction
  • Tumor Suppressor Proteins


  • 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.

publication date

  • October 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC3081654

Digital Object Identifier (DOI)

  • 10.1038/nn1767

PubMed ID

  • 16964251

Additional Document Info

start page

  • 1257

end page

  • 64


  • 9


  • 10