Measurements and simulations of microtubule growth imply strong longitudinal interactions and reveal a role for GDP on the elongating end DOI Creative Commons
Joseph M. Cleary, Tae‐il Kim, Annan SI Cook

и другие.

eLife, Год журнала: 2022, Номер 11

Опубликована: Апрель 14, 2022

Microtubule polymerization dynamics result from the biochemical interactions of αβ-tubulin with polymer end, but a quantitative understanding has been challenging to establish. We used interference reflection microscopy make improved measurements microtubule growth rates and fluctuations in presence absence GTP hydrolysis. In hydrolysis, microtubules grew steadily very low fluctuations. These data were best described by computational model implementing slow assembly kinetics, such that rate elongation is primarily limited associations. With GTPase present, displayed substantially larger than expected based on no measurements. Our modeling showed these occurred because exposure GDP-tubulin end transiently 'poisoned' growth, yielding wider range compared only conditions. experiments point association kinetics (strong longitudinal interactions), drugs regulatory proteins alter could do so modulating either or dissociation tubulin tip. By causing slower at growing may be an important early event determining catastrophe.

Язык: Английский

Mechanisms of microtubule organization in differentiated animal cells DOI
Anna Akhmanova, Lukas C. Kapitein

Nature Reviews Molecular Cell Biology, Год журнала: 2022, Номер 23(8), С. 541 - 558

Опубликована: Апрель 5, 2022

Язык: Английский

Процитировано

134
Microtubule Targeting Agents in Disease: Classic Drugs, Novel Roles DOI Open Access
Linda Wordeman, Juan Jesus Vicente

Cancers, Год журнала: 2021, Номер 13(22), С. 5650 - 5650

Опубликована: Ноя. 12, 2021

Microtubule-targeting agents (MTAs) represent one of the most successful first-line therapies prescribed for cancer treatment. They interfere with microtubule (MT) dynamics by either stabilizing or destabilizing MTs, and in culture, they are believed to kill cells via apoptosis after eliciting mitotic arrest, among other mechanisms. This classical view MTA persisted many years. However, limited success drugs specifically targeting proteins, slow growing rate human tumors forces a reevaluation mechanism action MTAs. Studies from last decade suggest that killing efficiency MTAs arises combination interphase effects. Moreover, MTs have also been implicated therapeutically relevant activities, such as decreasing angiogenesis, blocking cell migration, reducing metastasis, activating innate immunity promote proinflammatory responses. Two key problems associated therapy acquired drug resistance systemic toxicity. Accordingly, novel effective being designed an eye toward toxicity without compromising efficacy promoting resistance. Here, we will review MTAs, signaling pathways affect, their impact on illnesses, promising new therapeutic applications these classic drugs.

Язык: Английский

Процитировано

107
Mechanisms underlying spindle assembly and robustness DOI
Venecia A. Valdez, Lila Neahring, Sabine Petry

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 24(8), С. 523 - 542

Опубликована: Март 28, 2023

Язык: Английский

Процитировано

47
Helical protein nanotubules assembled from sacrificial supramolecular polymers DOI

Linfei Ye,

Xiaoduo Dong, Chong Wang

и другие.

Nature Synthesis, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

Язык: Английский

Процитировано

2
The microtubule cytoskeleton in cardiac mechanics and heart failure DOI
Matthew A. Caporizzo, Benjamin L. Prosser

Nature Reviews Cardiology, Год журнала: 2022, Номер 19(6), С. 364 - 378

Опубликована: Апрель 19, 2022

Язык: Английский

Процитировано

64
The Four Causes: The Functional Architecture of Centromeres and Kinetochores DOI Open Access
Andrew D. McAinsh, Adèle L. Marston

Annual Review of Genetics, Год журнала: 2022, Номер 56(1), С. 279 - 314

Опубликована: Сен. 2, 2022

Kinetochores are molecular machines that power chromosome segregation during the mitotic and meiotic cell divisions of all eukaryotes. Aristotle explains how we think have knowledge a thing only when grasped its cause. In our case, to gain understanding kinetochore, four causes correspond questions must ask: (

Язык: Английский

Процитировано

54
Enhancing image resolution of confocal fluorescence microscopy with deep learning DOI Creative Commons

Boyi Huang,

Jia Li, Bowen Yao

и другие.

PhotoniX, Год журнала: 2023, Номер 4(1)

Опубликована: Янв. 5, 2023

Abstract Super-resolution optical imaging is crucial to the study of cellular processes. Current super-resolution fluorescence microscopy restricted by need special fluorophores or sophisticated systems, long acquisition and computational times. In this work, we present a deep-learning-based technique confocal microscopy. We devise two-channel attention network (TCAN), which takes advantage both spatial representations frequency contents learn more precise mapping from low-resolution images high-resolution ones. This scheme robust against changes in pixel size setup, enabling optimal model generalize different modalities unseen training set. Our algorithm validated on diverse biological structures dual-color actin-microtubules, improving resolution ~ 230 nm 110 nm. Last but not least, demonstrate live-cell revealing detailed dynamic instability microtubules.

Язык: Английский

Процитировано

34
Microtubule‐targeting agents for cancer treatment: Seven binding sites and three strategies DOI Creative Commons
Xingyu Wang, Benoı̂t Gigant,

Xi Zheng

и другие.

MedComm – Oncology, Год журнала: 2023, Номер 2(3)

Опубликована: Авг. 16, 2023

Abstract Microtubules are pivotal in diverse cellular functions encompassing cell signaling, morphology, intracellular trafficking, and mitosis/division. They validated targets for disease treatment, notably hematological cancers solid tumors. Microtubule‐targeting agents (MTAs) exert their effects by modulating microtubule dynamics, impeding proliferation, promoting death. Recent advances structural biology have unveiled novel perspectives investigating multiple binding sites mechanisms of action used MTAs. In this review, we first provide an overview the intricate structure dynamics microtubules. Then explore seven three primary strategies (stabilization, destabilization, degradation) harnessed Furthermore, introduce emerging domain microtubule‐targeting degraders, exemplified PROteolysis TArgeting Chimeras small‐molecule which enable precise degradation specific microtubule‐associated proteins implicated cancer pathogenesis. Additionally, discuss promising realm precision‐targeted approaches, including antibody–drug conjugates utilization photopharmacology Lastly, a comprehensive clinical applications therapies, assessing efficacy current challenges. We aim to global picture MTAs development as well insights into drug discovery treatment.

Язык: Английский

Процитировано

32
Phase separation of +TIP networks regulates microtubule dynamics DOI Creative Commons

Julie Miesch,

Robert T. Wimbish,

Marie‐Claire Velluz

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(35)

Опубликована: Авг. 21, 2023

Regulation of microtubule dynamics is essential for diverse cellular functions, and proteins that bind to dynamic ends can regulate network dynamics. Here, we show two conserved end-binding proteins, CLIP-170 EB3, undergo phase separation form dense liquid networks. When EB3 act together, the multivalency increases, which synergistically increases amount protein in phase. In vitro cells, these networks concentrate tubulin. vitro, presence microtubules, EB3/CLIP-170 enrich tubulin all along microtubule. this condition, growth speed up twofold frequency depolymerization events are strongly reduced compared conditions there no separation. Our data adds an additional layer regulation control

Язык: Английский

Процитировано

26
Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation DOI Creative Commons
Bruno Carmona, H. Susana Marinho,

Catarina Lopes Matos

и другие.

Biology, Год журнала: 2023, Номер 12(4), С. 561 - 561

Опубликована: Апрель 6, 2023

Microtubules (MTs), dynamic polymers of α/β-tubulin heterodimers found in all eukaryotes, are involved cytoplasm spatial organization, intracellular transport, cell polarity, migration and division, cilia biology. MTs functional diversity depends on the differential expression distinct tubulin isotypes is amplified by a vast number different post-translational modifications (PTMs). The addition/removal PTMs to α- or β-tubulins catalyzed specific enzymes allows combinatory patterns largely enriching biochemical biophysical properties MTs, creating code read proteins, including microtubule-associated proteins (MAPs), which allow cellular responses. This review focused tubulin-acetylation, whose roles continue generate debate. We travel through experimental data pointing α-tubulin Lys40 acetylation role as being MT stabilizer typical PTM long lived most recent data, suggesting that enhances flexibility alters mechanical preventing from aging characterized structural damage. Additionally, we discuss regulation acetyltransferases/desacetylases their impacts physiology. Finally, analyze how changes levels have been be general response stress they associated with several human pathologies.

Язык: Английский

Процитировано

25