Emerging roles for E3 ubiquitin ligases in neural development and disease

Neurodevelopment is an intricate process with highly regulated, overlapping stages including neuronal differentiation and axon guidance. Aberrations during these and other stages are tied to the etiology of neurodevelopmental disorders like Autism Spectrum Disorder, Angelman Syndrome, and X-linked I...

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Main Authors: Maya Hale, Greg J. Bashaw
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1557653/full
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author Maya Hale
Greg J. Bashaw
author_facet Maya Hale
Greg J. Bashaw
author_sort Maya Hale
collection DOAJ
description Neurodevelopment is an intricate process with highly regulated, overlapping stages including neuronal differentiation and axon guidance. Aberrations during these and other stages are tied to the etiology of neurodevelopmental disorders like Autism Spectrum Disorder, Angelman Syndrome, and X-linked Intellectual Disability. Ubiquitination is a dynamic and highly reversible post-translational modification conferred by E3 ubiquitin ligases. Recent discoveries have advanced the understanding of how substrate ubiquitination can guide protein localization, drive protein degradation, and alter protein post translational modifications. In this review, we highlight members of the RING and HECT E3 ligase families to discuss their novel roles in the molecular mechanisms regulating neurodevelopment. These findings are both instrumental for informing the future directions of neurodevelopmental research, and in expanding knowledge of intracellular mechanisms of protein trafficking. In addition, a deeper understanding of the molecular mechanisms of E3 ligase function in development promises to offer new insights into the pathogenesis of neurodevelopmental disorders.
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spelling doaj-art-6a01e39b3a1040d59200bb7182c435722025-08-20T03:12:31ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-05-011310.3389/fcell.2025.15576531557653Emerging roles for E3 ubiquitin ligases in neural development and diseaseMaya HaleGreg J. BashawNeurodevelopment is an intricate process with highly regulated, overlapping stages including neuronal differentiation and axon guidance. Aberrations during these and other stages are tied to the etiology of neurodevelopmental disorders like Autism Spectrum Disorder, Angelman Syndrome, and X-linked Intellectual Disability. Ubiquitination is a dynamic and highly reversible post-translational modification conferred by E3 ubiquitin ligases. Recent discoveries have advanced the understanding of how substrate ubiquitination can guide protein localization, drive protein degradation, and alter protein post translational modifications. In this review, we highlight members of the RING and HECT E3 ligase families to discuss their novel roles in the molecular mechanisms regulating neurodevelopment. These findings are both instrumental for informing the future directions of neurodevelopmental research, and in expanding knowledge of intracellular mechanisms of protein trafficking. In addition, a deeper understanding of the molecular mechanisms of E3 ligase function in development promises to offer new insights into the pathogenesis of neurodevelopmental disorders.https://www.frontiersin.org/articles/10.3389/fcell.2025.1557653/fullneural differentiationaxon guidanceneural developmental disordersE3 ubiquitin ligasecommissurelessNdfip
spellingShingle Maya Hale
Greg J. Bashaw
Emerging roles for E3 ubiquitin ligases in neural development and disease
Frontiers in Cell and Developmental Biology
neural differentiation
axon guidance
neural developmental disorders
E3 ubiquitin ligase
commissureless
Ndfip
title Emerging roles for E3 ubiquitin ligases in neural development and disease
title_full Emerging roles for E3 ubiquitin ligases in neural development and disease
title_fullStr Emerging roles for E3 ubiquitin ligases in neural development and disease
title_full_unstemmed Emerging roles for E3 ubiquitin ligases in neural development and disease
title_short Emerging roles for E3 ubiquitin ligases in neural development and disease
title_sort emerging roles for e3 ubiquitin ligases in neural development and disease
topic neural differentiation
axon guidance
neural developmental disorders
E3 ubiquitin ligase
commissureless
Ndfip
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1557653/full
work_keys_str_mv AT mayahale emergingrolesfore3ubiquitinligasesinneuraldevelopmentanddisease
AT gregjbashaw emergingrolesfore3ubiquitinligasesinneuraldevelopmentanddisease