Article
Genetics & Heredity
Austin P. Harvey, Chien-Hui Chuang, Eisuke P. Sumiyoshi, Bruce Bowerman
Summary: The complex of two regulators of microtubule stability, ZYG-9 and TAC-1, has multiple and separable requirements during acentrosomal oocyte spindle assembly. They promote the coalescence of early pole foci into a bipolar structure and maintain pole stability, both of which are essential for proper chromosome separation. ZYG-9 and TAC-1 are also required for spindle assembly during the second meiotic cell division.
Article
Biochemistry & Molecular Biology
Marin Barisic, Girish Rajendraprasad
Summary: Recent research has shown that in human cells, the continuous poleward motion of microtubules in mitotic spindles is driven by four mitotic kinesins, with specific contributions at different stages of mitosis. While the molecular mechanism behind this cellular phenomenon has been elucidated, the functional roles of microtubule poleward flux during cell division remain largely unknown.
Article
Biology
Ina Lantzsch, Che-Hang Yu, Yu-Zen Chen, Vitaly Zimyanin, Hossein Yazdkhasti, Norbert Lindow, Erik Szentgyoergyi, Ariel M. Pani, Steffen Prohaska, Martin Srayko, Sebastian Furthauer, Stefanie Redemann
Summary: Female meiotic spindles undergo significant morphological changes from metaphase to anaphase, with an increase in microtubule numbers, decrease in average length, and significant changes in microtubule lengths near the chromosome surface. Microtubule turnover is the major driver of spindle rearrangements, with a minor fraction of microtubules being severed in metaphase, mainly those in close contact with chromosomes. The mechanisms of microtubule severing in this transition appear to be dependent on katanin.
Review
Cell Biology
Shreyas Sridhar, Tatsuo Fukagawa
Summary: The assembly of functional kinetochore is crucial for accurate chromosome segregation during mitosis. Internal and external structures of kinetochore face multiple challenges, but linker proteins play an important role in force propagation and recruitment of outer kinetochore. Understanding these linkages and regulatory pathways is essential for understanding kinetochore structural diversity and plasticity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Maya I. Anjur-Dietrich, Colm P. Kelleher, Daniel J. Needleman
Summary: Chromosome segregation, driven by the spindle, is a crucial process in cell division. Extensive research on spindles in different systems over the past 150 years has revealed commonalities and contrasts. Understanding the sites of force generation and fundamental mechanical principles of chromosome segregation is essential, as conserved sites of force generation may interact differently in different spindles, leading to distinct mechanical mechanisms. Combining biophysical experiments, coarse-grained theories, and evolutionary genetics can enhance our understanding of chromosome segregation in the future.
Article
Cell Biology
Ellis L. Ryan, James Shelford, Teresa Massam-Wu, Richard Bayliss, Stephen J. Royle
Summary: The research identified TACC3 and clathrin as core members, and chTOG and GTSE1 as ancillary members of the complex. Additionally, PIK3C2A was shown not to be a part of the complex. Targeting the TACC3-clathrin interface or their microtubule-binding sites are the two most likely strategies to disrupt spindle stability mediated by this multiprotein complex.
JOURNAL OF CELL SCIENCE
(2021)
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
Cell Biology
Shimin Wang, Longfeng Yao, Wenjuan Zhang, Zihang Cheng, Can Hu, Hang Liu, Yanling Yan, Anbing Shi
Summary: The deficiency of SMAP-1 leads to mislocalization of apical and basolateral proteins on the trans-Golgi network (TGN), with SMAP-1 colocalizing with AP-1. The AP-1 complex regulates the TGN localization of SMAP-1, promoting the assembly of clathrin to ensure polarized conventional secretion in C. elegans intestinal epithelia.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Anja Bufe, Ana Garcia del Arco, Magdalena Hennecke, Anchel de Jaime-Soguero, Matthias Ostermaier, Yu-Chih Lin, Anja Ciprianidis, Janina Hattemer, Ulrike Engel, Petra Beli, Holger Bastians, Sergio P. Acebron
Summary: Canonical Wnt signaling is crucial for development and tissue renewal by regulating beta-catenin target genes, while non-canonical Wnt signaling is also involved in mitosis. This study identified the role of Wnt signaling in regulating KIF2A during cell division, which is essential for chromosome alignment. Dishevelled recruits KIF2A and Wnt signaling modulates KIF2A interaction with PLK1, highlighting the importance of Wnt signaling in cell division and genome maintenance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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.
Review
Cell Biology
Kruno Vukusic, Iva M. Tolic
Summary: This review discusses the significance of chromosome congression and alignment in mitosis, as well as the factors that can lead to misalignment and missegregation. It also highlights the protective mechanisms employed by cells to prevent erroneous kinetochore-microtubule interactions and aneuploidy.
Article
Medicine, Research & Experimental
Galip S. Aslan, Nicolas Jae, Yosif Manavski, Youssef Fouani, Mariana Shumliakivska, Lisa Kettenhausen, Luisa Kirchhof, Stefan Guenther, Ariane Fischer, Guillermo Luxan, Stefanie Dimmeler
Summary: The adult mammalian heart has limited regenerative capacity, while the neonatal heart fully regenerates during the first week of life. The long noncoding RNA (lncRNA) Malat1 has been identified as a key player in postnatal cardiac regeneration, regulating cardiomyocyte proliferation and binucleation. Malat1 deletion prevents heart regeneration, leading to a decline in cardiomyocyte proliferation and reparative angiogenesis.
Article
Cell Biology
Amy K. Clippinger, Teresa V. Naismith, Wonjin Yoo, Silvia Jansen, David J. Kast, Phyllis I. Hanson
Summary: ESCRTs are protein complexes that play a crucial role in membrane remodeling and endosomal trafficking. IST1, one of the proteins in this complex, is involved in a wider range of endosomal remodeling events. Our study confirms that IST1, together with its binding partner CHMP1B, contributes to the scission of early endosomal carriers and is important for the transport of transferrin receptor and mannose 6-phosphate receptor. We also found that IST1 interacts with SNX15, a protein known to regulate endosomal recycling. Our results provide insights into the role of IST1 in a subset of recycling pathways from the early endosome.
Review
Cell Biology
Saara Hamalisto, Jonathan Stahl-Meyer, Marja Jaaettela
Summary: Mitosis, a tightly regulated process in mammalian life, can still result in errors leading to chromosomal instabilities and malignancies. Recent discoveries have shown unexpected roles for autophagy and lysosomes in preserving genomic integrity during mitosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Marta Wasielak-Politowska, Pawel Kordowitzki
Summary: The fertility and reproductive lifespan of human females decrease with age, leading to a prolonged post-reproductive period. The availability and quality of oocytes in the ovary play a significant role in female reproduction. Advanced maternal age is associated with increased rates of sub- and infertility, aneuploidy, miscarriages, and birth defects. The spindle apparatus and chromosome segregation during oocyte maturation are crucial for proper reproductive outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Rodney Luwor, Andrew P. Morokoff, Stephanie Amiridis, Giovanna D'Abaco, Lucia Paradiso, Stanley S. Stylli, Hong P. T. Nguyen, Mark Tarleton, Kelly A. Young, Terence J. O'Brien, Phillip J. Robinson, Megan Chircop, Adam McCluskey, Nigel C. Jones
CANCER INVESTIGATION
(2019)
Article
Chemistry, Multidisciplinary
Matthew G. Alteen, Christina Gros, Richard W. Meek, David A. Cardoso, Jil A. Busmann, Gontran Sangouard, Matthew C. Deen, Hong-Yee Tan, David L. Shen, Cecilia C. Russell, Gideon J. Davies, Phillip J. Robinson, Adam McCluskey, David J. Vocadlo
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2020)
Article
Biochemistry & Molecular Biology
Hui Yi Chew, Priscila O. De Lima, Jazmina L. Gonzalez Cruz, Blerida Banushi, Godwins Echejoh, Lingbo Hu, Shannon R. Joseph, Benedict Lum, James Rae, Jake S. O'Donnell, Lilia Merida de Long, Satomi Okano, Brigid King, Rachael Barry, Davide Moi, Roberta Mazzieri, Ranjeny Thomas, Fernando Souza-Fonseca-Guimaraes, Matthew Foote, Adam McCluskey, Phillip J. Robinson, Ian H. Frazer, Nicholas A. Saunders, Robert G. Parton, Riccardo Dolcetti, Katharine Cuff, Jennifer H. Martin, Benedict Panizza, Euan Walpole, James W. Wells, Fiona Simpson
Article
Multidisciplinary Sciences
Rebecca C. Poulos, Peter G. Hains, Rohan Shah, Natasha Lucas, Dylan Xavier, Srikanth S. Manda, Asim Anees, Jennifer M. S. Koh, Sadia Mahboob, Max Wittman, Steven G. Williams, Erin K. Sykes, Michael Hecker, Michael Dausmann, Merridee A. Wouters, Keith Ashman, Jean Yang, Peter J. Wild, Anna deFazio, Rosemary L. Balleine, Brett Tully, Ruedi Aebersold, Terence P. Speed, Yansheng Liu, Roger R. Reddel, Phillip J. Robinson, Qing Zhong
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Cedric S. Tremblay, Sung Kai Chiu, Jesslyn Saw, Hannah McCalmont, Veronique Litalien, Jacqueline Boyle, Stefan E. Sonderegger, Ngoc Chau, Kathryn Evans, Loretta Cerruti, Jessica M. Salmon, Adam McCluskey, Richard B. Lock, Phillip J. Robinson, Stephen M. Jane, David J. Curtis
NATURE COMMUNICATIONS
(2020)
Correction
Multidisciplinary Sciences
Cedric S. Tremblay, Sung Kai Chiu, Jesslyn Saw, Hannah McCalmont, Veronique Litalien, Jacqueline Boyle, Stefan E. Sonderegger, Ngoc Chau, Kathryn Evans, Loretta Cerruti, Jessica M. Salmon, Adam McCluskey, Richard B. Lock, Phillip J. Robinson, Stephen M. Jane, David J. Curtis
NATURE COMMUNICATIONS
(2021)
Review
Hematology
Cedric S. Tremblay, Stephen B. Ting, Adam McCluskey, Phillip J. Robinson, David J. Curtis
Summary: Endocytosis plays a crucial role in controlling cellular processes and cellular responses to the microenvironment. Targeting therapeutic strategies based on endocytosis show promise for the treatment of hematological malignancies.
EXPERIMENTAL HEMATOLOGY
(2021)
Article
Chemistry, Medicinal
Luke R. Odell, Ngoc Chau, Cecilia C. Russell, Kelly A. Young, Jayne Gilbert, Phillip J. Robinson, Jennette A. Sakoff, Adam McCluskey
Summary: The study involved the synthesis of pyrimidine-based dynamin GTPase inhibitors, with di- and tri-substituted pyrimidines showing higher levels of dynamin inhibition and potentially stronger cytotoxicity. These inhibitors demonstrated a good correlation between dynamin inhibition and cytotoxicity in various cancer cell lines.
Article
Biochemical Research Methods
Stephen A. Wood, Peter G. Hains, Arnaud Muller, Melissa Hill, Susitha Premarathne, Mariyam Murtaza, Phillip J. Robinson, George D. Mellick, Alex M. Sykes
Summary: In this study, we quantified proteomic differences between healthy control and PD patient cells and identified the critical role of the unfolded protein response (UPR) in PD patients. PD patients with high amounts of PDIA6 and HYOU1 proteins were more sensitive to endoplasmic reticulum stress. These findings provide insight into underlying cellular dysfunctions in PD patients.
PROTEOMICS CLINICAL APPLICATIONS
(2022)
Article
Oncology
Emanuel Goncalves, Rebecca C. Poulos, Zhaoxiang Cai, Syd Barthorpe, Srikanth S. Manda, Natasha Lucas, Alexandra Beck, Daniel Bucio-Noble, Michael Dausmann, Caitlin Hall, Michael Hecker, Jennifer Koh, Howard Lightfoot, Sadia Mahboob, Iman Mali, James Morris, Laura Richardson, Akila J. Seneviratne, Rebecca Shepherd, Erin Sykes, Frances Thomas, Sara Valentini, Steven G. Williams, Yangxiu Wu, Dylan Xavier, Karen L. MacKenzie, Peter G. Hains, Brett Tully, Phillip J. Robinson, Qing Zhong, Mathew J. Garnett, Roger R. Reddel
Summary: The study analyzes the proteomes of multiple cancer cell lines through mass spectrometry and reveals thousands of cancer protein biomarkers that are not significant at the transcript level, demonstrating that the proteome has predictive power for drug response similar to the transcriptome.
Review
Biochemical Research Methods
Emma L. Boys, Jia Liu, Phillip J. Robinson, Roger R. Reddel
Summary: Tumor tissue processing methodologies combined with data-independent acquisition mass spectrometry (DIA-MS) can accurately analyze the proteome of multiple tumor samples, providing new insights into cancer classification, tumor biology, biomarkers, treatment response, and drug targets. However, these technologies have not yet been widely implemented in routine cancer clinical practice.
Article
Biochemical Research Methods
Rebecca C. Poulos, Zhaoxiang Cai, Phillip J. Robinson, Roger R. Reddel, Qing Zhong
Summary: Proteomic data are valuable for drug response prediction and biomarker discovery due to the direct interaction between most drugs and proteins in target cells. This review highlights the opportunities of combining large-scale proteomic data with drug-related research, focusing on oncology. Successful applications of drug response prediction using molecular data are discussed, along with the technical advances in data-independent acquisition mass spectrometry (DIA-MS) for biomarker discovery. The potential of machine learning in pharmacoproteomics and the challenges of clinical validation are also explored.
Article
Chemistry, Medicinal
Luke R. Odell, Mark J. Robertson, Kelly A. Young, Andrew B. McGeachie, Annie Quan, Phillip J. Robinson, Adam McCluskey
Summary: The Bis-T series of compounds are potent inhibitors of dynamin GTPase activity. However, their low cell permeability limits their activity. To overcome this, prodrug ester analogues were synthesized. Among them, propionic ester 4 showed the highest efficacy, as it could effectively cross the cell membrane and rapidly hydrolyze into the desired Bis-T-22.
Article
Chemistry, Medicinal
Peter J. Cossar, David Cardoso, Daniel Mathwin, Cecilia C. Russell, Beatrice Chiew, Michael P. Hamilton, Jennifer R. Baker, Kelly A. Young, Ngoc Chau, Phillip J. Robinson, Adam McCluskey
Summary: Wiskostatin is a specific and potent inhibitor of the N-WASP actin remodeling complex. It also inhibits dynamin GTPase activity and endocytosis.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Meeting Abstract
Oncology
Hui Yi Chew, Benedict Panizza, Caroline Cooper, Riccardo Dolcetti, Jim Coward, Adam McCluskey, Phillip J. Robinson, James W. Wells, Fiona Simpson
MOLECULAR CANCER RESEARCH
(2020)