Non-Canonical Roles of Protein Ubiquitination and Degradation in the Nervous System

Protein quality control and signal transduction are essential to neural function, where precise modulation of protein abundance and modification determines neural development, synaptic efficacy, cellular resilience, and learning capacity. Among posttranslational modifications, ubiquitination stands out as a versatile regulator. Traditionally recognized for marking proteins for degradation via lysine-linked homogenous chains, emerging evidence increasingly reveals alternative ubiquitin linkages, non-lysine targets, and ubiquitin-independent degradation routes. These newfound discoveries are transforming our understanding of their role in fine-tuning neural development, circuit function, and neurodegeneration. Yet, the functional implications of these non-canonical ubiquitination and degradation pathways remain largely unexplored within the nervous system, representing a pivotal frontier in cellular neurobiology.This Research Topic aims to showcase research discoveries that challenge classical paradigms of ubiquitin signaling and protein degradation, emphasizing their mechanistic diversity and relevance to brain physiology and pathology. By integrating molecular, structural, and systems-level studies, the collection seeks to bridge biochemistry, cell biology, and neurophysiology to elucidate unconventional ubiquitin-dependent and -independent pathways that shape neuronal function and disease processes.To advance the mechanistic understanding of ubiquitination and protein degradation beyond canonical models, we invite submissions that embrace methodological innovation and conceptual novelty across in vitro, in vivo, and computational systems. Themes of interest include, but are not limited to:• Substrate ubiquitination on non-lysine residues• Heterogeneous or mixed-chain assembly and their cellular outcomes• Functional diversity of unconventional ubiquitin linkages in neurons• Regulation of neuronal proteostasis by novel ubiquitination enzymes and adaptors• Structural and mechanistic characterization of non-canonical proteasomal pathways• Crosstalk between ubiquitination and lipid- or autophagy-based degradation routes• Spatial and temporal regulation of ubiquitin signaling in synaptic compartments Topic editors: Angela M Mabb, Seth Shatkin Margolis, Timothy J Jarome Source: https://www.frontiersin.org/research-topics/82747/non-canonical-roles-of-protein-ubiquitination-and-degradation-in-the-nervous-system