Article
Biology
William Conway, Robert Kiewisz, Gunar Fabig, Colm P. Kelleher, Hai-Yin Wu, Maya Anjur-Dietrich, Thomas Mueller-Reichert, Daniel J. Needleman
Summary: During eukaryotic cell division, the distribution of kinetochore microtubules (KMTs) in the mitotic spindle is crucial for accurate chromosome segregation. This study investigates the processes that give rise to the observed distribution of KMTs in human cells. The results suggest that KMTs grow away from kinetochores along defined trajectories, with longer KMTs growing more slowly than shorter ones, leading to a mathematical model of kinetochore-fiber self-organization in human mitotic spindles.
Review
Cell Biology
Joao Barbosa, Claudio E. Sunkel, Carlos Conde
Summary: This review provides an overview of the molecular strategies that monitor and fine-tune KT-MT attachment formation during mitosis, to ensure accurate segregation of sister chromatids. This process is crucial for safe mitotic progression.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aurelien Courtois, Shuhei Yoshida, Osamu Takenouchi, Kohei Asai, Tomoya S. Kitajima
Summary: This study demonstrates the importance of stable kinetochore-microtubule attachments in confining MTOC positions at spindle poles and limiting spindle elongation in acentriolar spindles. The gradual MTOC sorting process in the metaphase spindle is crucial for maintaining spindle integrity. Disruption of stable kinetochore-microtubule attachments leads to failure in MTOC confinement and spindle elongation termination.
Article
Cell Biology
Matthias Weiss, Anna Chanou, Tamas Schauer, Andrey Tvardovskiy, Stefan Meiser, Ann-Christine Koenig, Tobias Schmidt, Elisabeth Kruse, Henning Ummethum, Manuel Trauner, Marcel Werner, Maxime Lalonde, Stefanie M. Hauck, Antonio Scialdone, Stephan Hamperl
Summary: This study uses site-specific recombination and single-locus chromatin isolation to purify early-efficient (EE) and late-inefficient (LI) replication origins in Saccharomyces cerevisiae. By identifying the protein composition of chromatin regions surrounding these origins, the researchers discover the microtubule-binding Ask1/DASH complex as a factor regulating replication timing (RT) and chromosomal organization. Targeting Ask1 to specific origin sites advances RT, while global degradation of Ask1 or inhibiting microtubule dynamics alters the RT of a subset of origins.
Article
Biochemistry & Molecular Biology
Babhrubahan Roy, Janice Sim, Simon J. Y. Han, Ajit P. Joglekar
Summary: The study investigates the interaction between Spc105 and Kre28 in budding yeast KTs. The results show that Spc105 and Kre28 localize at the KT with a 1:1 stoichiometry, and their interaction is important for Spc105 turnover and mutual recruitment at the KTs.
Review
Cell Biology
Angela R. R. Bunning, Mohan L. L. Gupta Jr.
Summary: Accurate chromosome segregation is essential for cell and organismal viability. The mitotic spindle, composed mainly of dynamic microtubules, plays a crucial role in this process by forming a bipolar configuration and generating tension across sister kinetochores. Recent advances have shed light on the role of tension as a biophysical signal that ensures accurate chromosome segregation by destabilizing aberrant kinetochore-microtubule attachments and reinforcing correct connections.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Jonas Neblik, Abbna Kirupakaran, Christine Beuck, Joel Mieres-Perez, Felix Niemeyer, My-Hue Le, Ursula Telgheder, Jessica Felice Schmuck, Alexander Dudziak, Peter Bayer, Elsa Sanchez-Garcia, Stefan Westermann, Thomas Schrader
Summary: The binding of Ndc80 protein to microtubules is crucial for kinetochore-microtubule attachments and the proper distribution of genetic material during cell division. Developing small molecule inhibitors that disrupt this interaction is important for studying chromosome segregation mechanisms and potential therapeutic applications.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Cell Biology
Yan-Li Sun, Xue-Lin Wang, Lei-Lei Yang, Zhao-Jia Ge, Yong Zhao, Shi-Ming Luo, Wei Shen, Qing-Yuan Sun, Shen Yin
Summary: Paraquat can reduce female fertility in mice by impairing nuclear and cytoplasmic maturation of oocytes, leading to misaligned chromosomes during meiosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Neurosciences
Alexis T. Weiner, Pankajam Thyagarajan, Yitao Shen, Melissa M. Rolls
Summary: Microtubules play a crucial role in the structure and transport within neurons, serving as tracks for long-range transport mediated by dynein and kinesin. The constant demand for transport requires the presence of new microtubules throughout the cell, highlighting the importance of microtubule nucleation to maintain the neuronal microtubule array.
NEUROSCIENCE LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Benjamin Craske, Thibault Legal, Julie P. I. Welburn
Summary: In this study, we characterized the motility of human CENP-E in vitro and found that the full-length form exhibits longer run length and residency times on microtubules compared to motor truncations. We also discovered that the non-motor coiled-coil regions self-regulate the motor activity. These findings provide a useful tool to study the mechanistic basis of how human CENP-E drives chromosome congression and spindle organization.
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
Biochemical Research Methods
Evgenii Kliuchnikov, Artem Zhmurov, Kenneth A. Marx, Alex Mogilner, Valeri Barsegov
Summary: This article introduces a Stochastic Reaction-Diffusion-Dynamics Model for simulations of cellular mechanochemical processes with high spatial and temporal resolution. The model was applied to test the Search-and-Capture mechanism of mitotic spindle assembly, revealing factors that improve the accuracy of chromosome connections.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tatsuya Fukuyama, Lucan Yan, Masahito Tanaka, Megumi Yamaoka, Kei Saito, Shih-Chieh Ti, Chung-Chi Liao, Kuo-Chiang Hsia, Yusuke T. Maeda, Yuta Shimamoto
Summary: The spindle is a dynamic intracellular structure essential for chromosome segregation during cell division. It can exhibit varied shape morphologies through nonrandom, bistable self-organization paths. The emergence of different spindle shapes is influenced by both physical and molecular factors.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Olivera Mitevska, Pak Wing Lam, Lydia Daly, Philip Auckland
Summary: Mitotic cell division requires the formation of microtubule attachments for chromosome segregation and mitotic progression. The shedding of the fibrous corona, which is mediated by dynein, plays a crucial role in this process. Little is known about the regulation of dynein stripping and its response to attachment maturation.
JOURNAL OF CELL SCIENCE
(2023)
Article
Multidisciplinary Sciences
Maelys Loh, Antoine Guichet, Fred Bernard
Summary: Live cell imaging is crucial for understanding cellular and molecular mechanisms regulating organelle movements, cytoskeleton rearrangements, and polarity patterning. The Drosophila egg chamber serves as an excellent model system due to its multicellular structure and abundance of genetic tools, allowing for the study of nuclear migration mechanisms. By developing a live imaging protocol, the dynamic events of nucleus migration can be captured, providing insight into its role in determining polarity axes in embryos and adult flies.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Biochemistry & Molecular Biology
Giuseppe Ciossani, Katharina Overlack, Arsen Petrovic, Pim J. Huis in 't Veld, Carolin Koerner, Sabine Wohlgemuth, Stefano Maffini, Andrea Musacchio
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Marion E. Pesenti, Daniel Prumbaum, Philip Auckland, Charlotte M. Smith, Alex C. Faesen, Arsen Petrovic, Muriel Erent, Stefano Maffini, Satyakrishna Pentakota, John R. Weir, Yu-Chih Lin, Stefan Raunser, Andrew D. McAinsh, Andrea Musacchio
Article
Biology
Amal Alex, Valentina Piano, Soumitra Polley, Marchel Stuiver, Stephanie Voss, Giuseppe Ciossani, Katharina Overlack, Beate Voss, Sabine Wohlgemuth, Arsen Petrovic, Yaowen Wu, Philipp Selenko, Andrea Musacchio, Stefano Maffini
Article
Biology
Pim J. Huis in ' t Veld, Vladimir A. Volkov, Isabelle D. Stender, Andrea Musacchio, Marileen Dogterom
Article
Biochemistry & Molecular Biology
Lindsey A. Allan, Magda Camacho Reis, Giuseppe Ciossani, Pim J. Huis int Veld, Sabine Wohlgemuth, Geert J. P. L. Kops, Andrea Musacchio, Adrian T. Saurin
Article
Multidisciplinary Sciences
Valentina Piano, Amal Alex, Patricia Stege, Stefano Maffini, Gerardo A. Stoppiello, Pim J. Huis in't Veld, Ingrid R. Vetter, Andrea Musacchio
Summary: The open and closed topologies of HORMA-domain proteins are associated with inactive and active cellular pathways, respectively. CDC20, an impervious substrate, requires simultaneous docking on several sites of the catalytic complex in order to accelerate its binding to MAD2, promoting MCC assembly. This may define a paradigm for other HORMA-controlled systems.
Article
Multidisciplinary Sciences
Franziska Mueller, Alexandra Friese, Claudio Pathe, Richard Cardoso da Silva, Kenny Bravo Rodriguez, Andrea Musacchio, Tanja Bange
Summary: This study reveals that by inhibiting the N-α-acetyltransferase NatA, proteins with IBM-like motifs can be transformed into efficient IAP binders, leading to cellular apoptosis. Thus, acetylation of the amino-terminal IBM-like motifs in NatA substrates serves as a protective mechanism against IAPs.
Article
Multidisciplinary Sciences
Kai Walstein, Arsen Petrovic, Dongqing Pan, Birte Hagemeier, Dorothee Vogt, Ingrid R. Vetter, Andrea Musacchio
Summary: By reconstituting the human kinetochore component CENP-C, researchers have discovered a new structure and function, indicating that human kinetochores are formed by clustering multiple copies of a fundamental module, which may have important implications for transgenerational inheritance.
Article
Biochemistry & Molecular Biology
Andrea Musacchio
Summary: Molecular mechanistic biology has delved into the basic building blocks of life, uncovering their interactions and proposing strategies for biological processes. The concept of biomolecular phase separation emphasizes the driving force of interactions, but its validation is challenging. Highly specific interactions may be the main driver of subcellular compartment formation, while phase separation can be locally utilized in specific instances.
Article
Biochemistry & Molecular Biology
Pim J. Huis in 't Veld, Sabine Wohlgemuth, Carolin Koerner, Franziska Muller, Petra Janning, Andrea Musacchio
Summary: During cell division into mitosis, CDK1 and Cyclin-B complex phosphorylate proteins, altering their conformations and functions; to study the mitotic protein machinery, a pure and active kinase complex must be reconstituted in vitro; high activity of CDK1:Cyclin-B complex can be achieved through the activation of a Threonine residue in the CDK1 activation loop.
Article
Biochemistry & Molecular Biology
Marion E. Pesenti, Tobias Raisch, Duccio Conti, Kai Walstein, Ingrid Hoffmann, Dorothee Vogt, Daniel Prumbaum, Ingrid R. Vetter, Stefan Raunser, Andrea Musacchio
Summary: This study presents the structure of human CCAN and identifies some unique features, providing insights into the specific recognition mechanism of CENP-A nucleosome.
Article
Cell Biology
Ricardo Celestino, Jose B. Gama, Artur F. Castro-Rodrigues, Daniel J. Barbosa, Helder Rocha, Ennio A. d'Amico, Andrea Musacchio, Ana Xavier Carvalho, Joao H. Morais-Cabral, Reto Gassmann
Summary: The MAP kinase and motor scaffold JIP3 plays a role in preventing excessive accumulation of lysosomes in axons. The interaction between JIP3 and dynein and kinesin-1 is important for organelle clearance, but the specific mechanisms are not fully understood.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Cell Biology
Erica Di Cesare, Sara Moroni, Jessica Bartoli, Michela Damizia, Maria Giubettini, Carolin Koerner, Veronica Krenn, Andrea Musacchio, Patrizia Lavia
Summary: Conjugation with the small ubiquitin-like modifier (SUMO) mediates protein interactions of Aurora B at centromeres in prometaphase and metaphase, while being dispensable for functions exerted in cytokinesis. NUP358/RANBP2 is implicated in the formation and localization of Aurora B-SUMO products, adding a novel layer to the modulation of Aurora B functions during mitosis.
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
Biochemistry & Molecular Biology
Verena Cmentowski, Giuseppe Ciossani, Ennio d'Amico, Sabine Wohlgemuth, Mikito Owa, Brian Dynlacht, Andrea Musacchio
Summary: The RZZS complex and CENP-E are closely connected and reciprocally required for their own kinetochore recruitment and dynein localization to the corona.
