Nonequilibrium bending fluctuations reveal microtubule mechanicsin-vivoand their regulation by glutamylation DOI Creative Commons
Kengo Nishi, Sufi O. Raja, An Q. Pham

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Окт. 27, 2023

Abstract Cells can be described as active composite materials. The mechanical properties of cells are controlled by complex polymer networks and dynamically tuned for diverse cellular processes driven force-generating motor proteins. Microtubules the most rigid protein polymers in cytoskeleton, their material have been measured vitro bending or analyzing thermal fluctuations. Microtubule mechanics living extremely difficult to probe directly, while fluctuations interpret because they generated forces a surrounding cytoplasm with poorly understood properties. Here we introduce method measure elastic microtubules making use motor-generated that drive Bending dynamics governed three main factors: microtubule properties, cytoskeletal forces, response characteristics cytoplasm. We show theoretically that, when one factor independently determined, other two derived from observed Using this discovered polyglutamylation, post-translational modification enriched on arrays need withstand large such those axons cilia, increases stiffness cells. Our work provides theoretical experimental framework study regulation tubulin modifications effectors environments. approach extended aspect ratio structures endoplasmic reticulum mitochondrial network.

Язык: Английский

The Tubulin Code, from Molecules to Health and Disease DOI Creative Commons

Elizabeth D. McKenna,

Stephanie L. Sarbanes,

Steven W. Cummings

и другие.

Annual Review of Cell and Developmental Biology, Год журнала: 2023, Номер 39(1), С. 331 - 361

Опубликована: Окт. 16, 2023

Microtubules are essential dynamic polymers composed of α/β-tubulin heterodimers. They support intracellular trafficking, cell division, cellular motility, and other processes. In many species, both α-tubulin β-tubulin encoded by multiple genes with distinct expression profiles functionality. further diversified through abundant posttranslational modifications, which added removed a suite enzymes to form complex, stereotyped arrays. The genetic chemical diversity tubulin constitute code that regulates intrinsic microtubule properties is read effectors, such as molecular motors microtubule-associated proteins, provide spatial temporal specificity microtubules in cells. this review, we synthesize the rapidly expanding literature highlight limitations opportunities for field. As complex arrays underlie physiological processes, better understanding how cells employ has important implications human disease ranging from cancer neurological disorders.

Язык: Английский

Процитировано

47
Elongator is a microtubule polymerase selective for polyglutamylated tubulin DOI Creative Commons
Vicente J. Planelles-Herrero, Mariya Genova, Lara K. Krüger

и другие.

The EMBO Journal, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Elongator is a tRNA-modifying complex that regulates protein translation. Recently, moonlighting function of has been identified in regulating the polarization microtubule cytoskeleton during asymmetric cell division. induces symmetry breaking anaphase midzone by selectively stabilizing microtubules on one side spindle, contributing to downstream polarized segregation cell-fate determinants, and therefore fate determination. Here, we investigate how controls dynamics. binds both tip free GTP-tubulin heterodimers using two different subcomplexes, Elp123 Elp456, respectively. We show these activities must be coupled for decrease tubulin critical concentration elongation. As consequence, increases growth speed decreases catastrophe rate microtubules. Surprisingly, Elp456 subcomplex tails strong selectivity towards polyglutamylated tubulin. Hence, assembled become enriched with tubulin, as observed vitro, mouse Drosophila lines, well vivo Sensory Organ Precursor cells. Therefore, rewrites code growing microtubules, placing it at core cytoskeletal dynamics

Язык: Английский

Процитировано

1
Choroid plexuses carry nodal-like cilia that undergo axoneme regression from early adult stage DOI Creative Commons

Kim Hoa Ho,

Adrien Candat,

Valentina Scarpetta

и другие.

Developmental Cell, Год журнала: 2023, Номер 58(23), С. 2641 - 2651.e6

Опубликована: Окт. 26, 2023

Язык: Английский

Процитировано

11
Regulation of microtubule growth rates and their impact on chromosomal instability DOI
Lia Mara Gomes Paim, Susanne Bechstedt

Cell Cycle, Год журнала: 2025, Номер unknown, С. 1 - 20

Опубликована: Апрель 22, 2025

Microtubules are polymers of α/β tubulin dimers that build the mitotic spindle, which segregates duplicated chromosomes during cell division. Microtubule function is governed by dynamic instability, whereby cycles growth and shrinkage contribute to forces necessary for chromosome movement. Regulation microtubule velocity requires cycle-dependent changes in expression, localization activity microtubule-associated proteins (MAPs) as well post-translational modifications modulate dynamics. It has become clear optimal velocities required proper segregation ploidy maintenance. Suboptimal rates can result from altered MAPs could lead aneuploidy, possibly disrupting establishment bundles at kinetochores altering mechanical sister chromatid segregation. Future work using high-resolution, low-phototoxicity microscopy novel fluorescent markers will be invaluable obtaining deeper mechanistic insights into how processes

Язык: Английский

Процитировано

0
Tubulin code eraser CCP5 binds branch glutamates by substrate deformation DOI
Jiayi Chen, Elena A. Zehr, James M. Gruschus

и другие.

Nature, Год журнала: 2024, Номер 631(8022), С. 905 - 912

Опубликована: Июль 17, 2024

Язык: Английский

Процитировано

3
Polyglutamylation of microtubules drives neuronal remodeling DOI Open Access
Antoneta Gavoci,

Anxhela Zhiti,

Michaela Rusková

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 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.

Язык: Английский

Процитировано

2
Microtubule function and dysfunction in the nervous system DOI Open Access
Eun‐Hae Jang,

Harryn Choi,

Eun‐Mi Hur

и другие.

Molecules and Cells, Год журнала: 2024, Номер unknown, С. 100111 - 100111

Опубликована: Сен. 1, 2024

Язык: Английский

Процитировано

1
The C. elegans deglutamylase CCPP-6 does not operate redundantly with CCPP-1 in gross cilia integrity. DOI

Abigail S Klimas,

Jessica A. Dominguez,

Bhumi P Shah

и другие.

PubMed, Год журнала: 2023, Номер 2023

Опубликована: Янв. 1, 2023

Tubulin glutamylation is a reversible modification of the microtubules that regulates cilia stability and function. The addition glutamates to microtubule catalyzed by members TTLL family enzymes, while removal carried out cytosolic carboxypeptidase (CCP) enzymes. C. elegans has two deglutamylating CCPP-1 CCPP-6 . required for ciliary function in worm, however dispensable integrity. To investigate redundancy between enzymes we made ccpp-1 ( ok1821 ); ccpp-6 ok382 ) double mutant. mutant shows normal viability, dye-filling phenotypes are not worse than single mutant, suggesting do redundantly

Язык: Английский

Процитировано

2
Elongator is a microtubule polymerase selective for poly-glutamylated tubulin DOI Creative Commons
Vicente J. Planelles-Herrero, Mariya Genova, Alice Bittleston

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Май 10, 2023

Elongator is a tRNA-modifying complex that regulates the fidelity of protein translation. Recently, moonlighting function has been identified in regulating polarization microtubule cytoskeleton during asymmetric cell division. induces symmetry breaking anaphase midzone by selectively stabilizing microtubules on one side spindle. This polarizes segregation signalling endosomes containing cell-fate determinants to only daughter cell, thus contributing fate determination. Here, we unravelled molecular mechanism which controls dynamics. binds simultaneously tip and also free GTP-tubulin heterodimers via their C-terminal tails. thereby locally increases tubulin concentration at ends, stabilizes increasing growth speed decreasing catastrophe rate. We show Elp123 Elp456 subcomplexes bind heterodimers, respectively, these activities must be coupled for stabilize microtubules. Surprisingly, found strong selectivity towards polyglutamylated dimers. Hence, assembled become enriched with tubulin. Therefore, can rewrite code growing microtubules, placing it core cytoskeletal dynamics

Язык: Английский

Процитировано

1
γ‐Glutamylation of Isopropylamine by Fermentation DOI Creative Commons
Leonie Benninghaus,

Laura Zagami,

Giulio Tassini

и другие.

ChemBioChem, Год журнала: 2023, Номер 25(2)

Опубликована: Ноя. 21, 2023

Abstract Glutamylation yields N ‐functionalized amino acids in several natural pathways. γ‐Glutamylated may exhibit improved properties for their industrial application, e. g., as taste enhancers or peptide drugs. γ‐Glutamyl−isopropylamide (GIPA) can be synthesized from isopropylamine (IPA) and l ‐glutamate. In Pseudomonas sp. strain KIE171, GIPA is an intermediate the biosynthesis of ‐alaninol (2‐amino‐1‐propanol), a precursor fluorochinolone antibiotic levofloxacin chloroacetanilide herbicide metolachlor. this study, fermentative production with metabolically engineered putida KT2440 using γ‐glutamylmethylamide synthetase (GMAS) Methylorubrum extorquens was established. Upon addition IPA during growth glycerol carbon source shake flasks, recombinant produced up to 21.8 mM GIPA. fed‐batch bioreactor cultivations, accumulated titer 11 g L −1 product yield 0.11 volumetric productivity 0.24 h . To best our knowledge, first

Язык: Английский

Процитировано

1