Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails DOI
Ezekiel C. Thomas, Jeffrey K. Moore

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(3)

Published: Dec. 17, 2024

The tubulin code hypothesis predicts that tails create programs for selective regulation of microtubule-binding proteins, including kinesin motors. However, the molecular mechanisms determine and their relevance in cells are poorly understood. We report budding yeast kinesin-5 motors by β-tubulin tail. Cin8, but not Kip1, requires tail recruitment to mitotic spindle, creating a balance both spindle efficient progression. identify negatively charged patch mediates interaction with Cin8. Using vitro reconstitution genetically modified tubulin, we demonstrate increases Cin8 plus-end-directed velocity processivity. Finally, positively amino-terminal extension coordinates interactions Our work identifies mechanism underlying closely related how this promotes proper function spindle.

Language: Английский

Structural switching of tubulin in the microtubule lattice DOI Creative Commons
Y. Gómez Maqueo Chew, Robert A. Cross

Biochemical Society Transactions, Journal Year: 2025, Volume and Issue: 53(01)

Published: Feb. 5, 2025

Microtubule (MT) dynamic instability, a cycle of growth, catastrophe, shrinkage and rescue, is driven by the switching tubulin between two structural states, one stabilised GTP other GDP. Recent work has uncovered ancient origins this switch revealed further fundamental elements microtubule whereby can be brought about range allosteric effectors, propagate deep within lattice assembled MTs, profoundly affect MT function. Here, we review evidence for discuss current ideas its mechanisms.

Language: Английский

Citations

0
SPY Interacts With Tubulin and Regulates Abscisic Acid‐Induced Stomatal Closure in Arabidopsis DOI Creative Commons
Tongtong Liu, Pan Wang, Zixuan Wang

et al.

Plant Direct, Journal Year: 2025, Volume and Issue: 9(4)

Published: April 1, 2025

ABSTRACT Sugars are important both as an energy source and a signaling cue. In Arabidopsis thaliana , SPINDLY (SPY) is the bona fide O ‐fucosylation transferase that links sugar with various plant growth development processes. Previously, spy was shown to display strong salt drought tolerance phenotype. Herein we confirmed phenotype further studied its mechanism. We found abscisic acid (ABA) elevated SPY expression in guard cells, involved ABA‐induced stomatal closure. show regulates rearrangement of microtubule cytoskeleton cells. Moreover, reorganization enhanced mutants. Mechanistically, interacts α‐tubulin1 (TUA1) yeast‐two hybrid, bimolecular fluorescence complementation split luciferase imaging assays, indicating TUA1 may be ‐fucosylated by SPY. Our work line notion has many substrates diverse processes plants, also unearths key mechanism how glycosylation stomata movement via cytoskeleton.

Language: Английский

Citations

0
CEP162: A critical regulator of ciliary transition zone assembly and its implications in ciliopathies DOI Creative Commons
Jun Yin,

J. Z. Bai,

Xiaochong He

et al.

Journal of Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 19(2)

Published: April 23, 2025

Language: Английский

Citations

0
MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement DOI Creative Commons
Michael V. Tran,

Daria Khuntsariya,

Richard D. Fetter

et al.

Developmental Cell, Journal Year: 2023, Volume and Issue: 59(2), P. 199 - 210.e11

Published: Dec. 29, 2023

Language: Английский

Citations

8
Microtubule-binding domains in Katanin p80 subunit are essential for severing activity in C. elegans DOI Creative Commons
Eva Beaumale, Lucie Van Hove, Lionel Pintard

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(4)

Published: Feb. 8, 2024

Microtubule-severing enzymes (MSEs), such as Katanin, Spastin, and Fidgetin play essential roles in cell division neurogenesis. They damage the microtubule (MT) lattice, which can either destroy or amplify MT cytoskeleton, depending on cellular context. However, little is known about how they interact with their substrates. We have identified microtubule-binding domains (MTBD) required for Katanin function C. elegans. a heterohexamer of dimers containing catalytic subunit p60 regulatory p80, both are female meiotic spindle assembly. Here, we report that p80-like(MEI-2) dictates binding to MTs via two MTBDs composed basic patches. Substituting these patches reduces MTs, compromising its meiotic-spindle Structural alignments p80s from different species revealed evolutionarily conserved, even if specific amino acids involved vary. Our findings highlight critical importance (p80) providing complex.

Language: Английский

Citations

3
Tubulin code eraser CCP5 binds branch glutamates by substrate deformation DOI
Jiayi Chen, Elena A. Zehr, James M. Gruschus

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8022), P. 905 - 912

Published: July 17, 2024

Language: Английский

Citations

3
How neurons maintain their axons long-term: an integrated view of axon biology and pathology DOI Creative Commons
Gaynor A. Smith, Sean T. Sweeney, Cahir J. O’Kane

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: July 26, 2023

Axons are processes of neurons, up to a metre long, that form the essential biological cables wiring nervous systems. They must survive, often far away from their cell bodies and century in humans. This requires self-sufficient biology including structural proteins, organelles, membrane trafficking, metabolic, signalling, translational, chaperone, degradation machinery—all maintaining homeostasis energy, lipids, signalling networks reactive oxygen species calcium. Axon maintenance also involves specialised cytoskeleton cortical actin-spectrin corset, bundles microtubules provide highways for motor-driven transport components organelles virtually all above-mentioned processes. Here, we aim conceptual overview key aspects axon physiology, homeostatic they form. can be derailed, causing axonopathies through ageing, trauma, poisoning, inflammation or genetic mutations. To illustrate which malfunctions lead axonopathies, focus on axonopathy-linked subcellular defects caused by Based these descriptions backed our comprehensive data mining genes linked neural disorders, describe ‘dependency cycle local homeostasis’ as an integrative model explain why very different causes trigger similar providing new ideas drive quest strategies able battle devastating diseases.

Language: Английский

Citations

7
Polyglutamylation of microtubules drives neuronal remodeling DOI Open Access
Antoneta Gavoci,

Anxhela Zhiti,

Michaela Rusková

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 12, 2024

Abstract Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. The cytoskeleton is critical for this process, as microtubule loss enzymatic severing an early step across many species. However, how microtubule-severing enzymes, such spastin, are activated in specific neuronal compartments remains unknown. Here, we reveal that polyglutamylation, a posttranslational tubulin modification enriched neurons, plays instructive role developmental by tagging microtubules severing. Motor neuron-specific gene deletion enzymes add or remove polyglutamylation—TTLL glutamylases vs. CCP deglutamylases—accelerates delays neuromuscular synapse neurotransmission-dependent manner. This mechanism not to peripheral but also operates central circuits, e.g., the hippocampus. Thus, polyglutamylation acts rheostat morphology connectivity.

Language: Английский

Citations

2
TUBB4A Inhibits Glioma Development by Regulating ROS-PINK1/Parkin-Mitophagy Pathway DOI

Xueru Xi,

Suqin Chen,

Xiaoli Zhao

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 4, 2024

Language: Английский

Citations

2
VASH2 enhances KIF3C-mediated EGFR-endosomal recycling to promote aggression and chemoresistance of lung squamous cell carcinoma by increasing tubulin detyrosination DOI Creative Commons
Jing Wang, Pengpeng Liu, Rui Zhang

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(10)

Published: Oct. 23, 2024

Lung squamous cell carcinoma (LUSC) is associated with high mortality and has few therapeutic options. Chemotherapy remains the main treatment for LUSC patients, but multi-drug resistance become dominant challenge in failure of chemotherapy various cancers. Therefore, effective strategy patients an urgent unmet need. Here, we found vasohibin-2 (VASH2) was a prognostic biomarker VASH2 promoted malignant biological behaviors cells chemoresistance by increasing detyrosination α-tubulin. The level detyrosinated-tubulin negatively patient prognosis. Blocking tubulin carboxypeptidase (TCP) activity inhibited xenograft tumor growth improved efficacy paclitaxel vivo. Results revealed that VASH2-induced increase boosted binding kinesin family member 3C (KIF3C) to microtubules enhanced KIF3C-dependent endosomal recycling EGFR, leading prolonged activation PI3K/Akt/mTOR signaling. This study demonstrated not only also promising target LUSC, which offers novel insight combination EpoY, TCP inhibitor, may be patients.

Language: Английский

Citations

2