BDNF controls phosphorylation and transcriptional networks governing cytoskeleton organization and axonal regeneration DOI Creative Commons
Jose Norberto S. Vargas, Anna‐Leigh Brown,

Kai Sun

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 6, 2023

SUMMARY Axonal degeneration underlies neuromuscular disorders and neuropathies. Dysregulation of neurotrophic factors, such as brain-derived factor (BDNF), in the peripheral nervous system has long been established to exacerbate axonopathy. However, molecular programs controlled by BDNF that facilitate axonal regeneration transport are not well-understood. Here, we unravel transcriptomic phosphorylation landscape shaped human iPSC-derived motor neurons. Using SLAM-Seq, reveal stimulation increases global transcription rate neurons governs gene regulatory networks converge with those engaged during repair/outgrowth. Phosphoproteomic analyses demonstrate remodels cytoskeletal-binding proteins, especially structural microtubule-associated proteins. Importantly, localized axonal-specific activation ERK1/2 is necessary for enhance neurotrophin-containing signaling endosomes potentiate after axotomy. Collectively, this work unveils a novel paradigm positions core regulator transcriptional driving HIGHLIGHTS SLAM-seq reveals increased modulates outgrowth/regeneration proteins BDNF-ERK1/2 controls

Language: Английский

BDNF controls phosphorylation and transcriptional networks governing cytoskeleton organization and axonal regeneration DOI Creative Commons
Jose Norberto S. Vargas, Anna‐Leigh Brown,

Kai Sun

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 6, 2023

SUMMARY Axonal degeneration underlies neuromuscular disorders and neuropathies. Dysregulation of neurotrophic factors, such as brain-derived factor (BDNF), in the peripheral nervous system has long been established to exacerbate axonopathy. However, molecular programs controlled by BDNF that facilitate axonal regeneration transport are not well-understood. Here, we unravel transcriptomic phosphorylation landscape shaped human iPSC-derived motor neurons. Using SLAM-Seq, reveal stimulation increases global transcription rate neurons governs gene regulatory networks converge with those engaged during repair/outgrowth. Phosphoproteomic analyses demonstrate remodels cytoskeletal-binding proteins, especially structural microtubule-associated proteins. Importantly, localized axonal-specific activation ERK1/2 is necessary for enhance neurotrophin-containing signaling endosomes potentiate after axotomy. Collectively, this work unveils a novel paradigm positions core regulator transcriptional driving HIGHLIGHTS SLAM-seq reveals increased modulates outgrowth/regeneration proteins BDNF-ERK1/2 controls

Language: Английский

Citations

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