title: A receptor for activated C kinase is part of messenger ribonucleoprotein complexes associated with polyA-mRNAs in neurons.
abstract: 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 PKCbeta2 in vitro by phosphatidylserine/diacylglycerol or in hippocampal slices by metabotropic glutamate receptor stimulation increased the amount of RACK1/PKCbeta2 associated with polysome-bound polyA-mRNAs. In vitro, PKCbeta2 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 PKCbeta2 to mRNP complexes bound to polyA-mRNAs is involved in activity-triggered control of protein synthesis.
authors.affiliation: Beckman Institute/Neuronal Pattern Analysis, University of Illinois, Urbana, Illinois 61801, USA. angenstein@ifn-magdeburg.de
authors.forename: Frank
authors.initials: F
authors.lastname: Angenstein
authors.forename: Anne M
authors.initials: AM
authors.lastname: Evans
authors.forename: Robert E
authors.initials: RE
authors.lastname: Settlage
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Moran
authors.forename: Shuo-Chien
authors.initials: SC
authors.lastname: Ling
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Klintsova
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Shabanowitz
authors.forename: Donald F
authors.initials: DF
authors.lastname: Hunt
authors.forename: William T
authors.initials: WT
authors.lastname: Greenough
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000737:chemistry; D004075:Diglycerides / Q000494:pharmacology; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism; D011061:Poly A / Q000378:metabolism; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism*; D013347:Subcellular Fractions / Q000737:chemistry; D014404:Tubulin / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D004075:Diglycerides; D020536:Enzyme Activators; D007527:Isoenzymes; D046911:Macromolecular Substances; D010718:Phosphatidylserines; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D012261:Ribonucleoproteins; D014404:Tubulin; C026452:messenger ribonucleoprotein; D011061:Poly A; D011493:Protein Kinase C; D064546:Protein Kinase C beta