Physical basis of large microtubule aster growth

eLife, Год журнала: 2016, Номер 5

Опубликована: Ноя. 28, 2016

Microtubule asters - radial arrays of microtubules organized by centrosomes play a fundamental role in the spatial coordination animal cells. The standard model aster growth assumes fixed number originating from centrosomes. However, morphology this does not scale with cell size, and we recently found evidence for non-centrosomal microtubule nucleation. Here, combine autocatalytic nucleation polymerization dynamics to develop biophysical growth. Our predicts that expand as traveling waves recapitulates all major aspects With increasing rate, an explosive transition stationary growing discontinuous jump velocity nonzero value. Experiments frog egg extract confirm main theoretical predictions. results suggest observed large fish amphibian eggs are meshwork short, unstable maintained provide paradigm assembly robust evolvable polymer networks.

Язык: Английский

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ICP0 Dismantles Microtubule Networks in Herpes Simplex Virus-Infected Cells

PLoS ONE, Год журнала: 2010, Номер 5(6), С. e10975 - e10975

Опубликована: Июнь 8, 2010

Infected-cell protein 0 (ICP0) is a RING finger E3 ligase that regulates herpes simplex virus (HSV) mRNA synthesis, and strongly influences the balance between latency replication of HSV. For 25 years, nuclear functions ICP0 have been subject intense scrutiny. To obtain new clues about ICP0's mechanism action, we constructed HSV-1 viruses expressed GFP-tagged ICP0. our surprise, both wild-type were predominantly observed in cytoplasm HSV-infected cells. Although exclusively during immediate-early phase HSV infection, further analysis revealed translocated to early where it triggered previously unrecognized process; dismantled microtubule network host cell. A mutant efficiently bundled microtubules, but failed disperse bundles. Synthesis proved be necessary sufficient disrupt networks transfected Plant animal encode many proteins reorganize microtubules. However, this first report viral stability. Intriguingly, several cellular ligases orchestrate disassembly reassembly mitosis. Our results suggest serves dual role life cycle, acting as regulator synthesis later, cytoplasm, dismantle cell's preparation for virion and/or egress.

Язык: Английский

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Mechanical regulation of cortical microtubules in plant cells

New Phytologist, Год журнала: 2023, Номер 239(5), С. 1609 - 1621

Опубликована: Июнь 29, 2023

Summary All living organisms are subjected to mechanical forces at all times. It has been reported that mechanics regulate many key cellular processes, including cell polarity establishment, division and gene expression, as a physical signal in both animal plant development. Plant cells exposed several types of stresses, ranging from turgor‐driven tensile force modified by heterogeneous growth directions rates between neighbouring cells, the environment such wind rain, for which they have developed adaptive mechanisms. Increasing evidence revealed stresses markedly influence alignment cortical microtubules (CMTs) among other effects. CMTs able reorient response single‐cell tissue levels always align with maximal stress direction. In this review, we discussed known potential molecules pathways involved regulation stresses. We also summarized available techniques allowed perturbation. Finally, highlighted questions remaining be addressed emerging field.

Язык: Английский

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Structures and mechanisms of AAA+ protein complexes in DNA processing

Current Opinion in Structural Biology, Год журнала: 2025, Номер 92, С. 103056 - 103056

Опубликована: Май 6, 2025

AAA+ proteins are a large family of ATPases involved in myriad cellular activities. Recent advances proteins, especially cryoEM structures these complex with their substrates, have provided key insights into how they function. Here we review recent progress structural studies and mechanistic understanding DNA processing, including gene transcription, replication, repair/recombination transposition. Using few selected examples, show act on both protein peptides, which often enclosed the pores hexamers. We propose that using to translocate peptide partially unfold substrate is an effective strategy disassembling assembled complex. Further, several although as asymmetric hexamers active form, adopt range oligomers for functions.

Язык: Английский

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Microtubule-binding domains in Katanin p80 subunit are essential for severing activity in C. elegans

The Journal of Cell Biology, Год журнала: 2024, Номер 223(4)

Опубликована: Фев. 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.

Язык: Английский

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14-3-3 protein augments the protein stability of phosphorylated spastin and promotes the recovery of spinal cord injury through its agonist intervention

eLife, Год журнала: 2023, Номер 12

Опубликована: Сен. 12, 2023

Axon regeneration is abortive in the central nervous system following injury. Orchestrating microtubule dynamics has emerged as a promising approach to improve axonal regeneration. The severing enzyme spastin essential for development and through remodeling of arrangement. To date, however, little known regarding mechanisms underlying action neural after spinal cord Here, we use glutathione transferase pulldown immunoprecipitation assays demonstrate that 14-3-3 interacts with spastin, both vivo vitro, via Ser233 phosphorylation. Moreover, show protects from degradation by inhibiting ubiquitination pathway upregulates spastin-dependent ability. Furthermore, agonist Fusicoccin (FC-A) promotes neurite outgrowth vitro which needs activation. Western blot immunofluorescence results revealed protein upregulated neuronal compartment injury vivo. In addition, administration FC-A not only locomotor recovery, but also nerve contusion lateral hemisection models; application inhibitor spastazoline successfully reverses these phenomena. Taken together, indicate molecular switch regulates levels, small molecule effectively mediates recovery mice requires participation.

Язык: Английский

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Ultrasensitivity of microtubule severing due to damage repair

iScience, Год журнала: 2024, Номер 27(2), С. 108874 - 108874

Опубликована: Янв. 11, 2024

Microtubule-based cytoskeletal structures aid in cell motility, polarization, and intracellular transport. These functions require a coordinated effort of regulatory proteins which interact with microtubule cytoskeleton distinctively. In-vitro experiments have shown that free tubulin can repair nanoscale damages microtubules created by severing proteins. Based on this observation, we theoretically analyze as competition between the processes damage spreading tubulin-induced repair. We demonstrate model is quantitative agreement in-vitro predict existence critical concentration above becomes rare, fast, sensitive to tubulin. show sensitivity leads dramatic increase dynamic range steady-state lengths when varied, are controlled severing. Our work demonstrates how synergy microtubule-associated bring about specific dynamical properties microtubules.

Язык: Английский

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The katanin A-subunits KATNA1 and KATNAL1 act co-operatively in mammalian meiosis and spermiogenesis to achieve male fertility

Development, Год журнала: 2023, Номер 150(22)

Опубликована: Окт. 26, 2023

Katanins, a class of microtubule-severing enzymes, are potent M-phase regulators in oocytes and somatic cells. How the complex evolutionarily crucial, male mammalian meiotic spindle is sculpted remains unknown. Here, using multiple single double gene knockout mice, we reveal that canonical katanin A-subunit KATNA1 its close paralogue KATNAL1 together execute aspects meiosis. We show collectively regulate spindle, cytokinesis midbody abscission, addition to diverse spermatid remodelling events, including Golgi organisation, acrosome manchette formation. also define KATNAL1-specific roles sperm flagellum development, regulation sperm-epithelial disengagement. Finally, proteomic approaches, KATNA1, KATNB1 testis interactome, which includes network cytoskeletal vesicle trafficking proteins. Collectively, presence paralogs spermatogenesis allows for 'customised cutting' via neofunctionalisation protective buffering redundancy.

Язык: Английский

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Male mammalian meiosis and spermiogenesis is critically dependent on the shared functions of the katanins KATNA1 and KATNAL1

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Ноя. 12, 2022

Summary Katanin microtubule severing enzymes are potent M-phase regulators in oocytes and somatic cells. How the complex, evolutionarily critical, male mammalian meiotic spindle is sculpted remains unknown. Here, using multiple single double gene knockout mice, we reveal that canonical katanin A-subunit, KATNA1, its close paralogue, KATNAL1, together execute aspects of meiosis. We show KATNA1 KATNAL1 collectively regulate spindle, cytokinesis midbody abscission, addition to diverse spermatid remodelling events, including Golgi organisation, acrosome manchette formation. also define KATNAL1-specific roles sperm flagella development, regulation, sperm-epithelial disengagement. Finally, proteomic approaches KATNB1 testis interactome, which includes a network cytoskeletal vesicle trafficking proteins. Collectively, presence A-subunit paralogs spermatogenesis allows for ‘customized cutting’ via neofunctionalization protective buffering redundancy.

Язык: Английский

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Progresses and prospects in microtubule depolymerizing Kinesin-13

Chinese Science Bulletin (Chinese Version), Год журнала: 2015, Номер 60(20), С. 1896 - 1905

Опубликована: Июль 1, 2015

Microtubules are important component of cytoskeletons.Dynamic regulations microtubules related to cellular physiological processes.Recently, there many proteins underlying assembly or disassembly, in which Kinesin-13s subfamily is widely studied.It reported that these kinesins play a key role control mitosis, regulation cilia and axonal growth pruning.In this review, we will discuss the depolymerizing mechanisms Kinesin-13, comparison analysis Kinesin-13's biological functions different model organisms.

Язык: Английский

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