Selective regulation of agrin mRNA induction and alternative splicing in PC12 cells by Ras-dependent actions of nerve growth factor.

The Journal of Biological Chemistry
M A SmithR A Maue

Abstract

The extracellular matrix protein agrin plays an important role in the formation and maintenance of the neuromuscular junction. However, regulation of agrin gene expression and pre-mRNA splicing, important in determining the biological actions of agrin, is not well understood. To begin to identify mechanisms controlling agrin expression, quantitative polymerase chain reaction techniques were used to analyze the effect of growth factors on the expression of agrin mRNA isoforms in rat pheochromocytoma (PC12) cells. Agrin transcripts in untreated cells lacked inserts in the Y and Z sites (agriny0z0), encoding agrin isoforms with low acetylcholine receptor aggregating activity and a primarily non-neuronal tissue distribution. Transcripts encoding isoforms with high aggregating activity and neuronal tissue distribution (agriny4z8, agriny4z11, and agriny4z19) were not detected. Treatment of PC12 cells with nerve growth factor (NGF) caused a significant increase in total agrin mRNA. In contrast, exposure to epidermal growth factor had no effect. Analysis of alternative splicing of agrin mRNA revealed that NGF elicited a specific increase in agriny4 and agrinz8 mRNAs that did not occur in the presence of epidermal growth factor, insulin...Continue Reading

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Citations

Jul 28, 2001·Progress in Neurobiology·P J Grabowski, D L Black
Aug 3, 2001·The EMBO Journal·S Weg-RemersH König
Mar 11, 2003·Annual Review of Biochemistry·Douglas L Black
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Dec 29, 2000·The Journal of Biological Chemistry·O StossS Stamm
Jun 22, 2006·Journal of Cell Science·Anabella Srebrow, Alberto R Kornblihtt

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