Cyclic AMP/GMP-dependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning

Makoto Nishiyama, Akemi Hoshino, Lily Tsai, John R. Henley, Yoshio Goshima, Marc Tessier-Lavigne, Mu-ming Poo and Kyonsoo Hong ()
Additional contact information
Makoto Nishiyama: New York University School of Medicine
Akemi Hoshino: New York University School of Medicine
Lily Tsai: New York University School of Medicine
John R. Henley: University of California at Berkeley
Yoshio Goshima: Yokohama City University School of Medicine
Marc Tessier-Lavigne: Stanford University
Mu-ming Poo: University of California at Berkeley
Kyonsoo Hong: New York University School of Medicine

Nature, 2003, vol. 423, issue 6943, 990-995

Abstract: Abstract Signalling by intracellular second messengers such as cyclic nucleotides and Ca2+ is known to regulate attractive and repulsive guidance of axons by extracellular factors1,2. However, the mechanism of interaction among these second messengers in determining the polarity of the guidance response is largely unknown. Here, we report that the ratio of cyclic AMP to cyclic GMP activities sets the polarity of netrin-1-induced axon guidance: high ratios favour attraction, whereas low ratios favour repulsion. Whole-cell recordings of Ca2+ currents at Xenopus spinal neuron growth cones indicate that cyclic nucleotide signalling directly modulates the activity of L-type Ca2+ channels (LCCs) in axonal growth cones. Furthermore, cGMP signalling activated by an arachidonate 12-lipoxygenase metabolite3 suppresses LCC activity triggered by netrin-1, and is required for growth-cone repulsion mediated by the DCC–UNC5 receptor complex4. By linking cAMP and cGMP signalling and modulation of Ca2+ channel activity in growth cones, these findings delineate an early membrane-associated event responsible for signal transduction during bi-directional axon guidance.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/nature01751 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:423:y:2003:i:6943:d:10.1038_nature01751

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01751

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().