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Role of KIS kinase in synaptic plasticity

AutorPedraza, Neus; Ortiz, Raúl; Aldea, Marti ; Gallego, Carme
Fecha de publicación7-jul-2013
Citación10th International Conference: Intracellular RNA Localization and Localized Translation (2013)
ResumenOur research group is interested in the study of the molecular mechanisms involved in synaptic plasticity. Particularly we are interested in the regulation of protein synthesis at synapses. KIS was first identified as a kinase that interacts with stathmin, a phosphoprotein that controls microtubule dynamics with a role in neuritic development. KIS is the only known protein kinase that possesses a U2AF homology motif (UHM), which is found immediately C-terminal to the kinase motif. Although the serine/threonine kinase domain has little homology to known kinases, a K54A mutation in the putative active center of KIS ablates its kinase activity. The C-terminal region presents a 42% sequence similarity to U2AF65, a 65-kDa subunit of the splicing factor U2AF. KIS expression was detected in various tissues, but mainly in the central nervous system and its expression is increased over the course of embryonic development. We have published that KIS interacts with three proteins found in RNA granules: KIF3A, NonO and eEF1A. and it is found associated with 10 RNP-transported mRNAs in brain extracts. Recent experiments in our group have shown that the absence of KIS in hippocampal cells decreases the levels of glutamate receptors GluR1/2 and also the postsynaptic density protein PSD-95. Our results indicate that this regulation is at post-transcriptional level and interestingly CPEB3 dependent. On the other hand, functional analysis shows that KIS knockdown enhances small dendritic spines (filopodia and thin spines) and decreases considerably the amplitude of excitatory postsynaptic currents. With this background we hypothesize that KIS kinase may have a significant role in controlling the localized translation of specific mRNAs as a key mechanism in neuronal plasticity.
DescripciónTrabajo presentado en la 10th International Conference on Intracellular RNA Localization and Localized Translation, celebrado en Niagara-on-the-Lake, Canadá, del 7 al 12 de julio de 2013
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