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J. Neurosci. 22 (20): 8827-8837

Copyright © 2002 by the Society for Neuroscience.

The Journal of Neuroscience, October 15, 2002, 22(20):8827-8837

A Receptor for Activated C Kinase Is Part of Messenger Ribonucleoprotein Complexes Associated with PolyA-mRNAs in Neurons

Frank Angenstein1, Anne M. Evans2, Robert E. Settlage2, 4, Stewart T. Moran1, Shuo-Chien Ling1, Anna Y. Klintsova1, Jeffrey Shabanowitz2, Donald F. Hunt2, 3, and William T. Greenough1

1 Beckman Institute/Neuronal Pattern Analysis, University of Illinois, Urbana, Illinois 61801, Departments of 2 Chemistry and 3 Pathology, University of Virginia, Charlottesville, Virginia 22904, and 4 ProteoMS, LLC, Charlottesville, Virginia 22903

Long-lasting changes in synaptic functions after an appropriate stimulus require altered protein expression at the synapse. To restrict changes in protein composition to activated synapses, proteins may be synthesized locally as a result of transmitter receptor-triggered signaling pathways. Second messenger-controlled mechanisms that affect mRNA translation are essentially unknown. Here we report that a receptor for activated C kinase, RACK1, is a component of messenger ribonucleoprotein (mRNP) complexes. RACK1 is predominantly associated with polysome-bound, polyA-mRNAs that are being actively translated. We find it to be present in a complex with beta -tubulin and at least two mRNA-binding proteins, polyA-binding protein 1 and a 130 kDa polyA-mRNA binding protein (KIAA0217). Activation of PKCbeta 2 in vitro by phosphatidylserine/diacylglycerol or in hippocampal slices by metabotropic glutamate receptor stimulation increased the amount of RACK1/PKCbeta 2 associated with polysome-bound polyA-mRNAs. In vitro, PKCbeta 2 can phosphorylate a subset of polyA-mRNA-associated proteins that are also phosphorylated under in vivo conditions. On the basis of these findings plus the somatodendritic localization of RACK1, we hypothesize that metabotropic glutamate receptor-triggered binding of activated PKCbeta 2 to mRNP complexes bound to polyA-mRNAs is involved in activity-triggered control of protein synthesis.

Key words: translational control; messenger ribonucleoproteins; metabotropic glutamate receptor; protein kinase C; protein phosphorylation; polyA-mRNA; mass spectrometry

Copyright © 2002 Society for Neuroscience  0270-6474/02/22208827-11$05.00/0

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