The hnRNP and cytoskeletal protein raver1 contributes to synaptic plasticity.
Raver1 is an hnRNP protein that interacts with the ubiquitous splicing regulator PTB and binds to cytoskeletal components like alpha-actinin and vinculin/metavinculin. Cell culture experiments suggested that raver1 functions as corepressor in PTB-regulated splicing reactions and may thereby increase proteome complexity. To determine the role of raver1 in vivo, we inactivated the gene by targeted disruption in the mouse. Here we report that raver1-deficient mice develop regularly to adulthood and show no obvious anatomical or behavioral defects. In keeping with this notion, cells from raver1-null mice were indistinguishable from wild type cells and displayed normal growth, motility, and cytoskeletal architecture in culture. Moreover, alternative splicing of exons, including the model exon 3 of alpha-tropomyosin, was not markedly changed in mutant mice, suggesting that the role of raver1 for PTB-mediated exon repression is not absolutely required to generate splice variants during mouse development. Interestingly however, loss of raver1 caused significantly reduced plasticity of synapses on acute hippocampal slices, as elicited by electrophysiological measurements of markedly lower LTP and LTD in mutant neurons. Our results provide evidence that raver1 may play an important role for the regulation of neuronal synaptic plasticity, possibly by controlling especially the late LTP via posttranscriptional mechanisms.
Cell and Molecular Biology, Institute for Biochemistry and Biotechnology, Technical University of Braunschweig, Braunschweig, Germany.
Ines
I
Lahmann
Manuela
M
Fabienke
Berenike
B
Henneberg
Oliver
O
Pabst
Franz
F
Vauti
Daniel
D
Minge
Susanne
S
Illenberger
Brigitte M
BM
Jockusch
Martin
M
Korte
Hans-Henning
HH
Arnold
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology; D004594:Electrophysiology; D004622:Embryo, Mammalian; D005347:Fibroblasts; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000502:physiology*; D006624:Hippocampus; D017774:Long-Term Potentiation; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009687:Nuclear Proteins / Q000172:deficiency / Q000502:physiology*; D010641:Phenotype; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D013569:Synapses / Q000502:physiology*
D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C442838:Raver1 protein, mouse; D012261:Ribonucleoproteins