TY - JOUR
T1 - Calcium mediates bidirectional growth cone turning induced by myelin-associated glycoprotein
AU - Henley, John R.
AU - Huang, Kuo Hua
AU - Wang, Dennis
AU - Poo, Mu Ming
N1 - Funding Information:
This work was supported by grants from the NIH NINDS (M.-m.P.) and an NIH NRSA award (J.R.H.). We thank Scott Wong for helpful discussions and for purification of MAG and Liwen Wu for technical assistance. The authors declare that they have no competing financial interests.
PY - 2004/12/16
Y1 - 2004/12/16
N2 - Cytoplasmic second messengers, Ca2+ and cAMP, regulate nerve growth cone turning responses induced by many guidance cues, but the causal relationship between these signaling pathways has been unclear. We here report that, for growth cone turning induced by a gradient of myelin-associated glycoprotein (MAG), cAMP acts by modulating MAG-induced Ca2+ signaling. Growth cone repulsion induced by MAG was accompanied by localized Ca2+ signals on the side of the growth cone facing the MAG source, due to Ca2+ release from intracellular stores. Elevating cAMP signaling activity or membrane depolarization enhanced MAG-induced Ca 2+ signals and converted growth cone repulsion to attraction. Directly imposing high- or low-amplitude Ca2+ signals with an extracellular gradient of Ca2+ ionophore was sufficient to trigger either attractive or repulsive turning, respectively. Thus, distinct Ca 2+ signaling, which can be modulated by cAMP, mediates the bidirectional turning responses induced by MAG.
AB - Cytoplasmic second messengers, Ca2+ and cAMP, regulate nerve growth cone turning responses induced by many guidance cues, but the causal relationship between these signaling pathways has been unclear. We here report that, for growth cone turning induced by a gradient of myelin-associated glycoprotein (MAG), cAMP acts by modulating MAG-induced Ca2+ signaling. Growth cone repulsion induced by MAG was accompanied by localized Ca2+ signals on the side of the growth cone facing the MAG source, due to Ca2+ release from intracellular stores. Elevating cAMP signaling activity or membrane depolarization enhanced MAG-induced Ca 2+ signals and converted growth cone repulsion to attraction. Directly imposing high- or low-amplitude Ca2+ signals with an extracellular gradient of Ca2+ ionophore was sufficient to trigger either attractive or repulsive turning, respectively. Thus, distinct Ca 2+ signaling, which can be modulated by cAMP, mediates the bidirectional turning responses induced by MAG.
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U2 - 10.1016/j.neuron.2004.11.030
DO - 10.1016/j.neuron.2004.11.030
M3 - Article
C2 - 15603734
AN - SCOPUS:10444267294
SN - 0896-6273
VL - 44
SP - 909
EP - 916
JO - Neuron
JF - Neuron
IS - 6
ER -