title: Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates.
abstract: Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome.
authors: NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy.|Fondazione Umberto Veronesi, Piazza Velasca 5, 20122, Milano, Italy.
authors: I
authors: I
authors: Tonazzini
authors: NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy.
authors: S
authors: S
authors: Meucci
authors: Department of Neuroscience, ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Wytemaweg 80, 3000, CA, Rotterdam, The Netherlands.
authors: G M
authors: GM
authors: Van Woerden
authors: Department of Neuroscience, ENCORE Expertise Center for Neurodevelopmental Disorders, Erasmus MC, Wytemaweg 80, 3000, CA, Rotterdam, The Netherlands.
authors: Y
authors: Y
authors: Elgersma
authors: NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Piazza San Silvestro 12, 56127, Pisa, Italy.
authors: M
authors: M
authors: Cecchini
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D053144:Cell Nucleus Shape; D048430:Cell Shape; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D016501:Neurites / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency* / Q000378:metabolism
chemical_list: D014404:Tubulin; D025801:Ubiquitin; C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: Angelman syndrome; contact guidance; nanostructured materials; neurite; ubiquitin ligase E3a (Ube3a)