Abstract
The identification of tags that can specifically mark activated synapses is important for understanding how long-term synaptic changes can be restricted to specific synapses. The maintenance of synapse-specific facilitation inAplysiasensory to motor neuron cultures can be blocked by inhibitors of translation and by the drug rapamycin, which specifically blocks a signaling pathway that regulates phosphorylation of translational regulators. One important target of rapamycin is the phosphorylation and subsequent activation of S6 kinase. To test whether S6 kinase is the target for the ability of rapamycin to block synapse-specific facilitation inAplysia, we clonedAplysiaS6 kinase, its substrate S6, and the S6 kinase kinase phosphoinositide-dependent kinase 1 (PDK-1). Serotonin, which induces synapse-specific facilitation, increased phosphorylation ofAplysiaS6 kinase at threonine 399 in a rapamycin-sensitive manner inAplysiasynaptosomes. The phosphorylation of threonine 399 by 5-HT was independent of phosphoinositide-3 kinase, dependent on PKA and PKC, and occluded by the phosphatase inhibitor calyculin-A. 5-HT also increased S6 kinase activity and led to increased phosphorylation of S6 in synaptosomes. 5-HT increased levels of S6 in synaptosomes because of a rapamycin-sensitive increase in translation–stabilization of S6.AplysiaPDK-1 bound to and phosphorylatedAplysiaS6 kinase but only modulated phosphorylation of threonine 399 indirectly. These results suggest a mechanism by which the levels of translation factors can be increased specifically at activated synapses generating a long-lasting synaptic tag.
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Dates
Type | When |
---|---|
Created | 7 years, 5 months ago (April 5, 2018, 11:05 a.m.) |
Deposited | 1 year, 2 months ago (July 5, 2024, 3:27 p.m.) |
Indexed | 1 year, 2 months ago (July 5, 2024, 3:40 p.m.) |
Issued | 24 years, 7 months ago (Jan. 15, 2001) |
Published | 24 years, 7 months ago (Jan. 15, 2001) |
Published Online | 24 years, 7 months ago (Jan. 15, 2001) |
Published Print | 24 years, 7 months ago (Jan. 15, 2001) |
@article{Khan_2001, title={Serotonin Activates S6 Kinase in a Rapamycin-Sensitive Manner inAplysiaSynaptosomes}, volume={21}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.21-02-00382.2001}, DOI={10.1523/jneurosci.21-02-00382.2001}, number={2}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Khan, Asad and Pepio, Antonio M. and Sossin, Wayne S.}, year={2001}, month=jan, pages={382–391} }