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Novel Kidins220/ARMS splice isoforms: Potential specific regulators of neuronal and cardiovascular development

AutorSchmieg, Nathalie; Thomas, Claire; Yabe, Arisa; Lynch, David S.; Iglesias, Teresa ; Chakravarty, Probir; Schiavo, Giampietro
Fecha de publicación2015
EditorPublic Library of Science
CitaciónPLoS ONE 10(6): e0129944 (2015)
ResumenKidins220/ARMS is a transmembrane protein playing a crucial role in neuronal and cardiovascular development. Kidins220/ARMS is a downstream target of neurotrophin receptors and interacts with several signalling and trafficking factors. Through computational modelling, we found two potential sites for alternative splicing of Kidins220/ARMS. The first is located between exon 24 and exon 29, while the second site replaces exon 32 by a short alternative terminal exon 33. Here we describe the conserved occurrence of several Kidins220/ARMS splice isoforms at RNA and protein levels. Kidins220/ARMS splice isoforms display spatio-temporal regulation during development with distinct patterns in different neuronal populations. Neurotrophin receptor stimulation in cortical and hippocampal neurons and neuroendocrine cells induces specific Kidins220/ARMS splice isoforms and alters the appearance kinetics of the full-length transcript. Remarkably, alternative terminal exon splicing generates Kidins220/ARMS variants with distinct cellular localisation: Kidins220/ARMS containing exon 32 is targeted to the plasma membrane and neurite tips, whereas Kidins220/ARMS without exon 33 mainly clusters the full-length protein in a perinuclear intracellular compartment in PC12 cells and primary neurons, leading to a change in neurotrophin receptor expression. Overall, this study demonstrates the existence of novel Kidins220/ARMS splice isoforms with unique properties, revealing additional complexity in the functional regulation of neurotrophin receptors, and potentially other signalling pathways involved in neuronal and cardiovascular development.
Versión del editorhttp://dx.doi.org/10.1371/journal.pone.0129944
URIhttp://hdl.handle.net/10261/125033
DOI10.1371/journal.pone.0129944
Identificadoresdoi: 10.1371/journal.pone.0129944
issn: 1932-6203
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