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Medientyp:
E-Artikel
Titel:
Akt-Dependent Potentiation of L Channels by Insulin-Like Growth Factor-1 Is Required for Neuronal Survival
Beteiligte:
Blair, Leslie A. C.;
Bence-Hanulec, Kendra K.;
Mehta, Sunil;
Franke, Thomas;
Kaplan, David;
Marshall, John
Erschienen:
Society for Neuroscience, 1999
Erschienen in:The Journal of Neuroscience
Sprache:
Englisch
DOI:
10.1523/jneurosci.19-06-01940.1999
ISSN:
0270-6474;
1529-2401
Entstehung:
Anmerkungen:
Beschreibung:
<jats:p>The insulin-like growth factor-1 (IGF-1)/receptor tyrosine kinase recently has been shown to mediate neuronal survival and potentiate the activity of specific calcium channel subtypes; survival requires Akt, a serine/threonine kinase. We demonstrate here that Akt mediates the IGF-1-induced potentiation of L channel currents, but not that of N channels. Transient expression of wild-type, dominant–negative, and constitutively active forms of Akt in cerebellar granule neurons causes, respectively, no change in IGF-1/L channel potentiation, complete inhibition of potentiation, and a dramatic increase in basal L currents accompanied by the loss of ability to induce further increases. In no case is the IGF-1 potentiation of N currents affected. We additionally find that IGF-1 partially mediates granule neuron survival via L channel activity and that Akt-dependent L channel modulation is a necessary component. Interestingly, very brief exposure (1 min) to IGF-1 triggers nearly complete survival and requires L channel activity. These results strongly suggest that neuronal receptor tyrosine kinases can control long-term calcium-dependent processes via the rapid control of voltage-sensitive channels.</jats:p>