Review
Cell Biology
Abesh Bera, Mohan L. Gupta
Summary: Microtubules are dynamic polymers assembled from alpha- and beta-tubulin subunits, with diverse properties determined by different tubulin isotypes and posttranslational modifications. Research in microorganisms has provided valuable insights into the distinct properties of tubulin isotypes and their roles in facilitating specific cellular processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Allison Ogren, Sneha Parmar, Soumya Mukherjee, Samuel J. Gonzalez, Melissa Plooster, Mark McClellan, Anirudh G. Mannava, Elliott Davidson, Trisha N. Davis, Melissa K. Gardner
Summary: Kinesin-14 motors play a role in controlling microtubule lengths by interacting with microtubule plus-ends and walking towards the minus-end. The binding of Kinesin-14 motors to microtubule plus-ends results in a decrease in microtubule lifetime and elongation, while inhibition of Kinesin-14 minus-end-directed motility leads to extended interactions and stabilization of microtubule plus-ends. This study demonstrates the importance of Kinesin-14 motors in regulating microtubule dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Ivana Gasic
Summary: The genomes of higher eukaryotes contain a large tubulin gene superfamily with various isotypes. The expression and regulation of these isotypes in different cell types, as well as their impact on the biomechanical properties of the microtubule cytoskeleton, are still poorly understood. Recent studies shed light on the complex regulatory pathways involved in the expression and function of tubulin isotypes, particularly during development and in specialized cells. This review summarizes our current understanding of the regulation of tubulin isotype expression and its importance in building a customized microtubule network for cellular needs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Crystallography
Noemi Sanchez-Castro, Martha Alicia Palomino-Ovando, Pushpendra Singh, Satyajit Sahu, Miller Toledo-Solano, Jocelyn Faubert, J. Eduardo Lugo, Anirban Bandyopadhyay, Kanad Ray
Summary: Researchers proposed a model suggesting that each tubulin dimer in microtubules can act as the period unit of a one-dimensional crystal, enabling signal transmission and processing through electromagnetic sensing.
Article
Cell Biology
Lei Diao, Ming-Yi Liu, Yin-Long Song, Xu Zhang, Xin Liang, Lan Bao
Summary: The study found that microtubules composed of different alpha-tubulin isotypes exhibit differences in growth rate and catastrophe frequency, largely attributed to variations in their C-terminal tails. Compared to alpha 1A/beta 2A microtubules, alpha 1C/beta 2A microtubules display higher growth rate and lower catastrophe frequency, which can be explained by the differences in their C-terminal tails.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Review
Neurosciences
Graziella Cappelletti, Alessandra Maria Calogero, Chiara Rolando
Summary: This study discusses the importance of microtubule acetylation in controlling neuronal and glial function, as well as its role in neurodegenerative disorders. Research has found that microtubule acetylation is a key modification that controls intracellular transport and stability, potentially serving as a novel therapeutic intervention for diseases like Parkinson's.
NEUROSCIENCE LETTERS
(2021)
Review
Cell Biology
Elizabeth D. McKenna, Stephanie L. Sarbanes, StevenW. Cummings, Antonina Roll-Mecak
Summary: Microtubules, composed of alpha/beta-tubulin heterodimers, are essential dynamic polymers that play crucial roles in various cellular processes. The genetic and chemical diversity of tubulin constitute a tubulin code that regulates microtubule properties and affects cellular functions. Understanding how cells utilize the tubulin code has important implications for human diseases.
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Anastasiya Klebanovych, Stanislav Vinopal, Eduarda Draberova, Vladimira Sladkova, Tetyana Sulimenko, Vadym Sulimenko, Vera Vosecka, Libor Macurek, Agustin Legido, Pavel Draber
Summary: ER distribution relies on microtubules, and disruption of ER homeostasis activates the unfolded protein response, leading to ER remodeling. UFL1 and C53 interact with gamma-tubulin ring complex proteins and regulate microtubule nucleation in response to ER stress. These findings reveal a novel mechanism for alleviating ER stress through stimulation of centrosomal microtubule nucleation.
Article
Neurosciences
Chuanyan Yang, Xuezhu Chen, Chenxu Zhang, Xuejiao Lei, Yongling Lu, Yuhai Wang, Hua Feng, Tunan Chen, Yang Yang
Summary: This study aimed to investigate whether the upregulation of acetylated α-tubulin (a-Ac-Tub) could alleviate injury to dendritic spines in the penumbra area and motor dysfunction after ischemic stroke. Knockout of MEC17, the specific acetyltransferase of a-tubulin, in pyramidal neurons exacerbated dendritic spine injury and motor dysfunction after stroke. However, upregulation of MEC17 and treatment with tubastatin A (TBA) maintained mature dendritic spine density and alleviated motor dysfunction after stroke.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Chemistry, Medicinal
Yuntao Ma, Fernando Josa-Prado, Jacob Nathaniel Essif, Shuqi Liu, Shuo Li, Daniel Lucena-Agell, Peter YW. Chan, Kenneth Goossens, Rafael Hortiguela, Ruth Matesanz, Yingjie Wang, Federico Gago, Hongbo Wang, April Risinger, J. Fernando Diaz, Wei-Shuo Fang
Summary: Taxane class microtubule stabilizers are effective and widely used chemotherapeutics that induce tubulin assembly. A series of non-covalent taxanes were discovered, which showed essential cytotoxicity due to their ability to lock tubulin in the assembled conformation. Further exploration led to the discovery of a new series with improved binding affinity and efficacy against breast cancer cells after drug washout, but also increased systemic toxicity that required localized injection for potent and prolonged antitumor efficacy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Mattia Pavani, Paolo Bonaiuti, Elena Chiroli, Fridolin Gross, Federica Natali, Francesca Macaluso, Adam Poti, Sebastiano Pasqualato, Zoltan Farkas, Simone Pompei, Marco Cosentino Lagomarsino, Giulia Rancati, David Szuts, Andrea Ciliberto
Summary: Cells with blocked microtubule polymerization can eventually proliferate despite chromosome missegregation, and through laboratory evolution, they can regain the ability to form microtubules and become less sensitive to microtubule-depolymerizing drugs. The study identified recurrently mutated genes, particularly for tubulins and kinesins, as well as duplication of chromosome VIII, which allowed cells to compensate for the original mutation. Analysis revealed a consistent series of events in the development of resistance, indicating the importance of chromosome duplication followed by adaptive mutations in tubulins or kinesins.
Article
Neurosciences
Rita Pinto-Costa, Monica Mendes Sousa
Summary: Cytolinkers play a crucial role in ensuring the integration of different cytoskeleton components in neurons, which is essential for proper function and connectivity of high order circuits. Several cytoskeleton regulatory proteins with actin-microtubule crosslinking activity have been identified as important players in axon outgrowth and guidance.
NEUROSCIENCE LETTERS
(2021)
Article
Cell Biology
Kei K. Ito, Koki Watanabe, Haruki Ishida, Kyohei Matsuhashi, Takumi Chinen, Shoji Hata, Daiju Kitagawa
Summary: The study demonstrates that the cooperative maintenance of centriole engagement by Cep57 and Cep57L1 during interphase is crucial for controlling centriole copy number and ensuring proper chromosome segregation. Loss of Cep57 and Cep57L1 leads to premature centriole disengagement and subsequent errors in chromosome segregation.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Bibi Najma, Minu Varghese, Lev Tsidilkovski, Linnea Lemma, Aparna Baskaran, Guillaume Duclos
Summary: This paper investigates the origin of two distinct instabilities in active gels of biopolymers and molecular motors. Combining experiments and theory, it shows how to rationally design and control active materials with targeted elasticity and activity.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Andrew D. McAinsh, Geert J. P. L. Kops
Summary: The spindle assembly checkpoint (SAC) is crucial for correct chromosome segregation during cell division. It monitors the interaction of chromosomes with spindle microtubules and halts anaphase until all kinetochores are properly attached. Recent studies have provided insights into the dynamic signaling properties of SAC and its integration at mammalian kinetochores, which have multiple attachment points.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Respiratory System
Kirill Zhudenkov, Robert Palmer, Alexandra Jauhiainen, Gabriel Helmlinger, Oleg Stepanov, Kirill Peskov, Ulf G. Eriksson, Ulrika Wahlby Hamren
Summary: Joint modeling of FEV1 and exacerbation data in COPD clinical trials can increase statistical power and reveal the relationship between improved FEV1 and reduced exacerbation risk. However, the impact of improved FEV1 on exacerbation trial design is generally small, suggesting the need for further exploration of other longitudinal endpoints.
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(2021)
Article
Pharmacology & Pharmacy
Kirill Zhudenkov, Sergey Gavrilov, Alina Sofronova, Oleg Stepanov, Nataliya Kudryashova, Gabriel Helmlinger, Kirill Peskov
Summary: Clinical trials investigate treatment endpoints with measurements of biomarkers in early-phase studies and patient-reported outcomes in late-phase studies. A systematic trend in clinical trial data analytics and modeling has been observed, where retrospective data are integrated into a quantitative framework to support analyses of interim data and design of future studies. Joint modeling, an advanced statistical methodology, allows for investigating clinical trial outcomes by quantifying the association between biomarkers and event risk. A workflow for joint modeling using an exemplar dataset from non-small cell lung cancer studies is proposed and tested.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2022)
Article
Engineering, Biomedical
Artem K. Efremov, Mingxi Yao, Yuze Sun, Yee Han Tee, Michael P. Sheetz, Alexander D. Bershadsky, Boris Martinac, Jie Yan
Summary: This study verifies the mechanosensitivity of L-type Ca2+ channels in Filopodia and reveals the interplay between mechanical forces and Ca2+ signaling in Filopodia, providing novel mechanistic insights into the guidance function of Filopodia in cell migration.
Article
Biophysics
Yunxin Deng, Artem K. Efremov, Jie Yan
Summary: Proteins rely on specific interactions with binding partners for their biological functions. Proteins with multiple binding domains can significantly enhance both the binding affinity and specificity, as well as lower the working concentration range. Positive domain-domain cooperativity or the presence of a non-specific binding domain can decrease the working concentration range by increasing the binding affinity without compromising the binding specificity. The configuration of bound ligands shows concentration dependence, providing insights into phase-separation processes in living cells.
BIOPHYSICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Celine Alkemade, Harmen Wierenga, Vladimir A. Volkov, Magdalena Preciado Lopez, Anna Akhmanova, Pieter Rein ten Wolde, Marileen Dogterom, Gijsje H. Koenderink
Summary: This study reveals the mechanism of passive cross-linkers generating forces in the interaction between actin and microtubules, and experimentally verifies this process. The results demonstrate that passive cross-linkers can facilitate the transportation of actin filaments on microtubules, which is significant for cellular remodeling processes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biophysics
Artem K. Efremov, Ladislav Hovan, Jie Yan
Summary: The size of the nucleus affects DNA-protein interactions and chromatin structure, which is determined by the difference in surface tensions between the nuclear envelope and endoplasmic reticulum membrane, as well as the osmotic pressure exerted by cytosolic macromolecules. The cell nucleus also functions as a piezoelectric element, changing its electrostatic potential in a size-dependent manner and affecting the stability of nucleosomes.
BIOPHYSICAL JOURNAL
(2022)
Article
Biophysics
Felix Schwietert, Vladimir A. Volkov, Pim J. Huis in't Veld, Marileen Dogterom, Andrea Musacchio, Jan Kierfeld
Summary: In the mitotic spindle, microtubules attach to chromosomes via kinetochores, with the Ndc80 complex playing a crucial role in this process. The study reveals that Ndc80 complexes exhibit strain stiffening when subjected to tension, with effective stiffness increasing as tension builds up from depolymerizing microtubules. This behavior can be attributed to the specific architecture of the Ndc80 complex, thermal fluctuations of microtubules, and the bending elasticity of flaring protofilaments.
BIOPHYSICAL JOURNAL
(2022)
Article
Cell Biology
Ali Nick Maleki, Pim J. Huis in 't Veld, Anna Akhmanova, Marileen Dogterom, Vladimir A. Volkov
Summary: Microtubules are dynamic cytoskeletal filaments that can generate forces through polymerization and depolymerization. Proteins that interact with microtubule ends and facilitate force generation are essential for cellular processes. In this study, we propose a novel experimental approach using a fluorescent spring-shaped DNA origami molecule to estimate microtubule-generated forces. The DNA nanospring allows multiplexed force measurements and only requires basic laboratory equipment. We validate the performance of DNA nanosprings and demonstrate their utility in studying protein-mediated force generation during microtubule growth and shortening.
JOURNAL OF CELL SCIENCE
(2023)
Article
Cell Biology
Alexandra P. Navarro, Iain M. Cheeseman
Summary: This study identifies a minimal sequence sufficient for Golgi targeting and discovers a critical amino acid residue through mutational analysis, providing important insights into Golgi protein localization.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Cell Biology
Alexandra P. Navarro, Iain M. Cheeseman
Summary: The kinetochore, essential for proper chromosome segregation during cell division, is assembled on the CCAN platform. The phosphorylation of CENP-L and CENP-N controls the formation and localization of the CENP-LN complex in a cell cycle-dependent manner, indicating the importance of phosphorylation cycles in kinetochore dynamics.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Biochemistry & Molecular Biology
Luke Funk, Kuan-Chung Su, Jimmy Ly, David Feldman, Avtar Singh, Brittania Moodie, Paul C. Blainey, Iain M. Cheeseman
Summary: Understanding the roles of essential genes in cellular processes is crucial for understanding cellular growth, proliferation, and function. This study used CRISPR-Cas9-based screening and microscopy imaging to identify the contributions of over 5,000 genes to cellular organization and morphology. Analysis of millions of cells revealed measurable phenotypes for over 90% of gene knockouts, providing insights into specific cellular processes. Clustering of phenotypic similarities further revealed co-functional genes and predicted gene functions and associations. The study also identified genes with functional contributions to chromosome segregation. This work provides a detailed resource exploring the consequences of disrupting core cellular processes.
Article
Cell Biology
Renu Maan, Louis Reese, Vladimir A. Volkov, Matthew R. King, Eli O. van der Sluis, Nemo Andrea, Wiel H. Evers, Arjen J. Jakobi, Marileen Dogterom
Summary: Growing microtubule ends can organize end-tracking proteins into mixed composition comets. In a reconstituted fission yeast system, these proteins can form liquid-phase droplets in solution and at microtubule ends under crowding conditions. Motor-dependent comets consist of disordered networks that may facilitate non-stoichiometric accumulation of cargo Tip1, while autonomous comet formation requires specific disordered protein regions in Mal3. The enrichment of Tip1 at microtubule ends may be attributed to motor activity and multivalent interactions.
NATURE CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Soumitra Polley, Helen Mueschenborn, Melina Terbeck, Anna De Antoni, Ingrid R. Vetter, Marileen Dogterom, Andrea Musacchio, Vladimir A. Volkov, Pim J. Huis In 't Veld
Summary: During cell division, the Ndc80 complex plays a crucial role in linking chromosomes to spindle microtubules. This study demonstrates that the Ndc80 loop promotes direct interactions between adjacent Ndc80 complexes, which are necessary for stable end-on kinetochore-microtubule attachment and spindle assembly checkpoint satisfaction. Mutations in the loop impair these interactions and lead to cell arrest in mitosis.
Article
Cell Biology
Cyntha M. van den Berg, Vladimir A. Volkov, Sebastian Schnorrenberg, Ziqiang Huang, Kelly E. Stecker, Ilya Grigoriev, Sania Gilani, Kari-Anne M. Frikstad, Sebastian Patzke, Timo Zimmermann, Marileen Dogterom, Anna Akhmanova
Summary: CSPP1, a protein associated with cilia and centrosomes, preferentially binds to slowly growing or perturbed microtubule ends, stabilizing their structure. This study reveals the mechanisms by which CSPP1 regulates the elongation and stability of cilia and other microtubule-based structures by inhibiting microtubule growth and shortening.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Mary-Jane Tsang, Iain M. Cheeseman
Summary: Mitotic defects can activate the spindle-assembly checkpoint, leading to cell cycle arrest. Cells can escape this arrest through mitotic slippage if errors are not resolved. This study reveals that the duration of mitotic arrest is modulated by alternative CDC20 translational isoforms, and suggests that changes in CDC20 isoform ratios or translational control can affect mitotic arrest duration and anti-mitotic drug sensitivity, with potential implications for cancer diagnosis and treatment.