title: Novel Kidins220/ARMS Splice Isoforms: Potential Specific Regulators of Neuronal and Cardiovascular Development.
abstract: Kidins220/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.
authors.affiliation: Molecular Neuropathobiology Laboratory, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom; The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, United Kingdom.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Schmieg
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Thomas
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, United Kingdom.
authors.forename: Arisa
authors.initials: A
authors.lastname: Yabe
authors.affiliation: Molecular Neuropathobiology Laboratory, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom; Leonard Wolfson Centre for Experimental Neurology, University College London, 8 Queen Anne Street, London W1G 9LD, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Lynch
authors.affiliation: Instituto de Investigaciones Biomédicas "Alberto Sols" (CSIC-UAM), C/ Arturo Duperier, 4, Madrid 28029, Spain; CIBERNED (ISCIII), C/ Valderrebollo 5, Madrid 28031, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Iglesias
authors.affiliation: The Francis Crick Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, United Kingdom.
authors.forename: Probir
authors.initials: P
authors.lastname: Chakravarty
authors.affiliation: Molecular Neuropathobiology Laboratory, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.
authors.forename: Giampietro
authors.initials: G
authors.lastname: Schiavo
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002319:Cardiovascular System / Q000254:growth & development*; D005091:Exons / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C544017:Kidins220 protein, mouse; D008565:Membrane Proteins; D020033:Protein Isoforms; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA