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

The Role of Spastin in Axon Biology DOI Creative Commons
Ana Catarina Costa, Mónica Mendes Sousa

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Июль 5, 2022

Neurons are highly polarized cells with elaborate shapes that allow them to perform their function. In neurons, microtubule organization—length, density, and dynamics—are essential for the establishment of polarity, growth, transport. A mounting body evidence shows modulation cytoskeleton by microtubule-associated proteins fine tunes key aspects neuronal cell biology. this respect, severing enzymes—spastin, katanin fidgetin—a group bind generate internal breaks in lattice, emerging as modulators different model systems. review, we provide an integrative view on latest research demonstrating role spastin specifically context axonal We focus function regulation organization, transport, underlie its importance intricate control axon branching regeneration.

Язык: Английский

Процитировано

27

Tracer dynamics in one dimensional gases of active or passive particles DOI Creative Commons
Tirthankar Banerjee, Robert L. Jack, M. E. Cates

и другие.

Journal of Statistical Mechanics Theory and Experiment, Год журнала: 2022, Номер 2022(1), С. 013209 - 013209

Опубликована: Янв. 1, 2022

We consider one-dimensional systems comprising either active run-and-tumble particles (RTPs) or passive Brownian random walkers. These are noninteracting have hardcore exclusions. study the dynamics of a single tracer particle embedded in such system - this may be passive, with exclusion from environmental particles. In an environment, both and tracers show long-time subdiffusion: displacements scale as $t^{1/4}$ density-dependent prefactor that is independent type, differs corresponding result for passive-in-passive subdiffusion. environment particles, results recovered at low densities tracers, but transient caging effects slow motion higher densities, delaying onset any regime. For we find more complex outcomes, which depend on details dynamical discretization scheme. interpret these by studying density distribution around tracer. particular, sticking to cause it move slowly than interacting environments, while anomalous behaviour active-in-passive cases stems `snowplough' effect whereby large pile diffusive accumulates front RTP during ballistic run.

Язык: Английский

Процитировано

25

Intermediate Filaments in Cellular Mechanoresponsiveness: Mediating Cytoskeletal Crosstalk From Membrane to Nucleus and Back DOI Creative Commons
Anne-Betty Ndiaye, Gijsje H. Koenderink, M. Shemesh

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Апрель 11, 2022

The mammalian cytoskeleton forms a mechanical continuum that spans across the cell, connecting cell surface to nucleus via transmembrane protein complexes in plasma and nuclear membranes. It transmits extracellular forces interior, providing cues influence cellular decisions, but also actively generates intracellular forces, enabling probe remodel its tissue microenvironment. Cells adapt their gene expression profile morphology external provided by matrix adjacent cells as well cell-intrinsic changes cytoplasmic volume. is complex filamentous network of three interpenetrating structural proteins: actin, microtubules, intermediate filaments. Traditionally actin considered main contributor mechanosensitivity. This view now shifting owing mounting evidence cytoskeletal filaments have interdependent functions due crosstalk, with taking central role. In this Mini Review we discuss how crosstalk confers mechanosensitivity tissues, particular focus on role We propose composite structure, which regulates local stability organization all filament families at sub-cellular scale, mechanics adaptation scale.

Язык: Английский

Процитировано

24

Anti-tumor pharmacology of natural products targeting mitosis DOI Creative Commons

Manru Huang,

Caiyan Liu,

Yingying Shao

и другие.

Cancer Biology and Medicine, Год журнала: 2022, Номер 19(6), С. 1 - 28

Опубликована: Июнь 15, 2022

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation cancer cells is one cancer’s main characteristics, which closely associated with abnormal mitosis. Targeting mitosis effective method for treatment. This review summarizes several natural products anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, disadvantages typical compounds, including drug resistance, toxicity non-tumor tissues, poor aqueous solubility pharmacokinetic properties, are also discussed, together strategies address them. Improved understanding cell may pave way development treatment cancer.

Язык: Английский

Процитировано

24

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

Процитировано

23