RGD Reference Report - Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones. - Rat Genome Database

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Soluble adenylyl cyclase is required for netrin-1 signaling in nerve growth cones.

Authors: Wu, KY  Zippin, JH  Huron, DR  Kamenetsky, M  Hengst, U  Buck, J  Levin, LR  Jaffrey, SR 
Citation: Wu KY, etal., Nat Neurosci. 2006 Oct;9(10):1257-64. Epub 2006 Sep 10.
RGD ID: 2313171
Pubmed: (View Article at PubMed) PMID:16964251
DOI: Full-text: DOI:10.1038/nn1767

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.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component
axon  (IDA)
dendrite  (IDA)
growth cone  (IDA)
neuronal cell body  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Adcy10  (adenylate cyclase 10)


Additional Information