RESUMEN
Raver2 was identified as a novel member of the hnRNP family based on sequence homology within three RNA recognition motifs and its general domain organization reminiscent of the previously described raver1 protein. Like raver1, raver2 contains two putative nuclear localization signals and a potential nuclear export sequence, and also displays nucleo-cytoplasmic shuttling in a heterokaryon assay. In glia cells and neurons, raver2 localizes to the nucleus. Moreover, the protein interacts with polypyrimidine tract binding protein (PTB) suggesting that it may participate in PTB-mediated nuclear functions. In contrast to ubiquitously expressed raver1, raver2 exerts a distinct spatio-temporal expression pattern during embryogenesis and is essentially restricted to brain, lung, and kidney in the adult mouse.
Asunto(s)
Ribonucleoproteínas Nucleares Heterogéneas/química , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/metabolismo , Núcleo Celular/química , Núcleo Celular/metabolismo , Citoplasma/química , Citoplasma/metabolismo , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario , Ribonucleoproteínas Nucleares Heterogéneas/clasificación , Humanos , Ratones , Datos de Secuencia Molecular , Neuroglía/citología , Neuronas/química , Neuronas/metabolismo , Señales de Localización Nuclear , Proteínas Nucleares/metabolismo , Proteína de Unión al Tracto de Polipirimidina/análisis , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Transporte de Proteínas , Proteínas de Unión al ARN , Ribonucleoproteínas , Distribución TisularRESUMEN
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.