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| Research article summary (published 29 Nov 1998): |
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Specific agrin isoforms induce cAMP response element binding protein phosphorylation in hippocampal neurons.
Full Abstract
The synaptic basal lamina protein agrin is essential for the formation of neuromuscular junctions. Agrin mediates the postsynaptic clustering of acetylcholine receptors and regulates transcription in muscles. Agrin expression is not restricted to motor neurons but can be demonstrated throughout the CNS. The functional significance of agrin expression in neurons other than motor neurons is unknown. To test whether agrin triggers responses in neurons that lead to the activation of transcription factors, we have analyzed phosphorylation of the transcriptional regulatory site serine 133 of the transcription factor CREB (cAMP response element binding protein) in primary hippocampal neurons. Our results indicate that the neuronal (Ag4,8), but not the non-neuronal (Ag0,0), isoform of agrin induces CREB phosphorylation in hippocampal neurons. The kinetics of agrin- and BDNF-induced CREB phosphorylation are similar: peak levels are reached in minutes and are strongly reduced 2 hr later. Neuronal responses to agrin require extracellular calcium, and, in contrast to tyrosine kinase inhibitors, the specific inhibition of protein kinase A (PKA) does not affect agrin-evoked CREB phosphorylation. Our results show that hippocampal neurons specifically respond to neuronal agrin in a Ca2+-dependent manner and via the activation of tyrosine kinases.
Author information
Author/s: Ji, R R (RR); Böse, C M (CM); Lesuisse, C (C); Qiu, D (D); Huang, J C (JC); Zhang, Q (Q); Rupp, F (F);
Affiliation: Department of Neuroscience, School of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Grants: MH51158 (Agency:NIMH NIH HHS)
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in UNITED STATES. (Language: eng)
Reference: 1998-Dec; vol 18 (issue 23) : pp 9695-702
Dates: Created 1998/12/18; Completed 1998/12/18; Revised 2007/11/15;
PMID: 9822730, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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