Editorial: Pathways and Processes Underpinning Axonal Biology and Pathobiology DOI Creative Commons
Pabitra K. Sahoo, Dianna E. Willis, James N. Sleigh

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: March 23, 2022

EDITORIAL article Front. Mol. Neurosci., 23 March 2022Sec. Molecular Signalling and Pathways https://doi.org/10.3389/fnmol.2022.883244

Language: Английский

De-centralizing the Central Dogma: mRNA translation in space and time DOI Creative Commons
Ashley M. Bourke, Andre Schwarz, Erin M. Schuman

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(3), P. 452 - 468

Published: Jan. 19, 2023

As our understanding of the cell interior has grown, we have come to appreciate that most cellular operations are localized, is, they occur at discrete and identifiable locations or domains. These domains contain enzymes, machines, other components necessary carry out regulate these localized operations. Here, review features one such operation: localization translation mRNAs within subcellular compartments observed across types organisms. We describe conceptual advantages "ingredients" mechanisms local translation. focus on nature mRNAs, how travel get this process is regulated. also evaluate current protein synthesis machines (ribosomes) their cadre regulatory elements, factors.

Language: Английский

Citations

53
BDNF-dependent modulation of axonal transport is selectively impaired in ALS DOI Creative Commons
Andrew P. Tosolini, James N. Sleigh, Sunaina Surana

et al.

Acta Neuropathologica Communications, Journal Year: 2022, Volume and Issue: 10(1)

Published: Aug. 22, 2022

Abstract Axonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments, is needed for neuronal development, function, survival. Deficits in axonal have been detected at pre-symptomatic stages the SOD1 G93A TDP-43 M337V mouse models amyotrophic lateral sclerosis (ALS), suggesting that impairments this critical process are fundamental disease pathogenesis. Strikingly, ALS, fast motor neurons (FMNs) degenerate first whereas slow (SMNs) more resistant, a currently unexplained phenomenon. The main aim investigation was to determine effects brain-derived neurotrophic factor (BDNF) on vivo different α-motor neuron (MN) subtypes wild-type (WT) mice. We report despite displaying similar basal speeds, stimulation MNs with BDNF enhances trafficking signalling endosomes specifically FMNs. This BDNF-mediated enhancement also observed primary ventral horn cultures. However, FMNs display selective impairment symptomatic mice , refractory stimulation, phenotype embryonic neurons. Furthermore, upregulation classical non-pro-survival truncated TrkB p75 NTR receptors muscles, sciatic nerves, Schwann cells. Altogether, these data indicate cell- non-cell autonomous impaired MNs, thus identifying new key deficit ALS.

Language: Английский

Citations

40
Lost in local translation: TDP-43 and FUS in axonal/neuromuscular junction maintenance and dysregulation in amyotrophic lateral sclerosis DOI Creative Commons
Diana Piol,

Tessa Robberechts,

Sandrine Da Cruz

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(9), P. 1355 - 1380

Published: March 23, 2023

Language: Английский

Citations

26
Insulin signalling regulates Pink1 mRNA localization via modulation of AMPK activity to support PINK1 function in neurons DOI Creative Commons
J. Tabitha Hees,

Simone Wanderoy,

Jana Lindner

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(3), P. 514 - 530

Published: March 19, 2024

Abstract Mitochondrial quality control failure is frequently observed in neurodegenerative diseases. The detection of damaged mitochondria by stabilization PTEN-induced kinase 1 (PINK1) requires transport Pink1 messenger RNA (mRNA) tethering it to the mitochondrial surface. Here, we report that inhibition AMP-activated protein (AMPK) activation insulin signalling cascade prevents mRNA binding mitochondria. Mechanistically, AMPK phosphorylates anchor complex subunit SYNJ2BP within its PDZ domain, a phosphorylation site necessary for interaction with RNA-binding SYNJ2. Notably, loss association upon addition required PINK1 and function as ubiquitin mitophagy pathway, thus placing under metabolic control. Induction resistance vitro key genetic Alzheimer risk factor apolipoprotein E4 retains at proper activity, especially neurites. Our results identify switch controlling localization activity via neurons propose mechanistic connection between dysfunction.

Language: Английский

Citations

16
Intrinsic Burst-Blinking Nanographenes for Super-Resolution Bioimaging DOI Creative Commons
Xingfu Zhu, Qiang Chen, Hao Zhao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5195 - 5203

Published: Jan. 26, 2024

Single-molecule localization microscopy (SMLM) is a powerful technique to achieve super-resolution imaging beyond the diffraction limit. Although various types of blinking fluorophores are currently considered for SMLM, intrinsic remain rare at single-molecule level. Here, we report synthesis nanographene-based burst-blinking highly versatile SMLM. We image amyloid fibrils in air and pH solutions without any additive lysosome dynamics live mammalian cells under physiological conditions. In addition, labeling nascent proteins primary sensory neurons was achieved with azide-functionalized nanographenes via click chemistry. SMLM reveals higher local translation axonal branching unprecedented detail, while size foci remained similar throughout entire network. These results demonstrate potential drastically expand applicability imaging.

Language: Английский

Citations

13
Boosting peripheral BDNF rescues impaired in vivo axonal transport in CMT2D mice DOI Creative Commons
James N. Sleigh, David Villarroel‐Campos, Sunaina Surana

et al.

JCI Insight, Journal Year: 2023, Volume and Issue: 8(9)

Published: March 16, 2023

Gain-of-function mutations in the housekeeping gene GARS1, which lead to expression of toxic versions glycyl-tRNA synthetase (GlyRS), cause selective motor and sensory pathology characterizing Charcot-Marie-Tooth disease (CMT). Aberrant interactions between GlyRS mutants different proteins, including neurotrophin receptor tropomyosin kinase B (TrkB), underlie CMT type 2D (CMT2D); however, our pathomechanistic understanding this untreatable peripheral neuropathy remains incomplete. Through intravital imaging sciatic nerve, we show that CMT2D mice displayed early persistent disturbances axonal transport neurotrophin-containing signaling endosomes vivo. We discovered brain-derived neurotrophic factor (BDNF)/TrkB impairments correlated with disruption overall neuropathology inhibition pathway at nerve-muscle interface perturbed endosome wild-type axons. Accordingly, supplementation muscles BDNF, but not other neurotrophins, completely restored physiological neuropathic mice. Together, these findings suggest selectively targeting BDNF-boosting therapies could represent a viable therapeutic strategy for CMT2D.

Language: Английский

Citations

15
CLUH maintains functional mitochondria and translation in motoneuronal axons and prevents peripheral neuropathy DOI Creative Commons
Marta Zaninello, Tim Schlegel, Hendrik Nolte

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(22)

Published: May 29, 2024

Transporting and translating mRNAs in axons is crucial for neuronal viability. Local synthesis of nuclear-encoded mitochondrial proteins protects long-lived axonal mitochondria from damage; however, the regulatory factors involved are largely unknown. We show that CLUH, which binds encoding proteins, prevents peripheral neuropathy motor deficits mouse. CLUH enriched growth cone developing spinal motoneurons required their growth. The lack affects abundance target corresponding more prominently axons, leading to ATP cone. interacts with ribosomal subunits, translation initiation, ribosome recycling components preserves translation. Overexpression factor ABCE1 rescues mRNA defects, as well size, CLUH-deficient motoneurons. Thus, we demonstrate a role quality control translational regulation essential development long-term integrity function.

Language: Английский

Citations

6
Emerging implications for ribosomes in proximity to mitochondria DOI
Bar Cohen,

Adi Golani‐Armon,

Yoav Arava

et al.

Seminars in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 154, P. 123 - 130

Published: Jan. 13, 2023

Language: Английский

Citations

10
The node of Ranvier influences the in vivo axonal transport of mitochondria and signalling endosomes DOI Creative Commons
Andrew P. Tosolini, Federico Abatecola, Samuele Negro

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(11), P. 111158 - 111158

Published: Oct. 11, 2024

Language: Английский

Citations

3
Multi-organelle-mediated mRNA localization in neurons and links to disease DOI Creative Commons

Vance K. Bauer,

Max Koppers

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102332 - 102332

Published: March 7, 2025

Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation proteome in distal outposts neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial neuron maintenance, dysregulation these processes can contribute to neurological disease. Recently, organelles have emerged as key players regulating dendrites axons. In this review, we discuss current evidence open questions organelle-mediated localization. We highlight an emerging model which multiple create orchestrate a subcellular microenvironment that support selective seems essential maintaining organellar health, mutations many involved proteins lead various disorders.

Language: Английский

Citations

0