Article
Biochemistry & Molecular Biology
Tao Huang, Xinyue Wu, Shiyu Wang, Ziyou Bao, Yanling Wan, Ziqi Wang, Mengjing Li, Xiaochen Yu, Yue Lv, Zhaojian Liu, Xiangfeng Chen, Wai-Yee Chan, Fei Gao, Gang Lu, Zi-Jiang Chen, Hongbin Liu
Summary: RAD51 and DMC1 are meiotic recombinases that play critical roles in DNA double-strand break repair by homologous recombination. This study reveals that SPIDR is a scaffold protein involved in the regulation of RAD51/DMC1 on single-stranded DNA. Deletion of Spidr in male mice leads to complete meiotic arrest, accompanied by defects in synapsis and crossover formation, resulting in male infertility. In females, loss of Spidr leads to subfertility, but some Spidr(-/-) oocytes are able to complete meiosis. Importantly, fertility is partially rescued by ablation of the DNA damage checkpoint kinase CHK2 in Spidr(-/-) females but not in males. Thus, this study identifies SPIDR as an essential meiotic recombination factor in mammals.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Srividya Venkatramanan, Consuelo Ibar, Kenneth D. Irvine
Summary: The study reveals the important roles of TRIP6 and LIMD1 in mediating the effects of cytoskeletal tension on organ growth, with TRIP6 being crucial for the localization of LIMD1. Furthermore, the competition between focal adhesions and adherens junctions for key proteins needed to maintain attachments to contractile F-actin is highlighted.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Thor Eysteinsson, Andrea Garcia-Llorca, Arnar Oessur Hardarson, Daniela Vullo, Fabrizio Carta, Claudiu T. Supuran
Summary: Previous research has shown that carbonic anhydrase inhibitors (CAIs) can induce vasodilation in retinal arteriolar segments, but it is unclear which isoforms or mechanisms are responsible for this effect. In this study, four new CAIs that do not enter cell membranes but have high affinity for cytosolic and membrane-bound isoforms of CA were tested. None of these CAIs had a significant effect on arteriolar wall tension, while a membrane permeant CAI called benzolamide fully dilated all segments tested. This suggests that CAIs act as vasodilators through cellular mechanisms located in the cytoplasm of vascular cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Sara Gonzalez-Arranz, Isabel Acosta, Jesus A. Carballo, Beatriz Santos, Pedro A. San-Segundo
Summary: This study reveals the mechanism of polo-like kinase Cdc5 during meiotic prophase I to meiosis I transition, showing that its overexpression partially relieves the meiotic delay induced by the checkpoint. However, a mutant version lacking the N-terminal region fails to alleviate the delay. In addition, the double mutant exhibits an exacerbated meiotic block compared to the single mutant.
Article
Oncology
Laura C. Funk, Jun Wan, Sean D. Ryan, Charanjeet Kaur, Ruth Sullivan, Avtar Roopra, Beth A. Weaver
Summary: Chromosomal instability is a hallmark of cancer, with high levels of CIN causing cell death and tumor suppression. The tumor suppressor p53 is not required for high CIN-induced tumor suppression, as demonstrated by pharmacological induction of high CIN resulting in cell death independently of p53 function.
MOLECULAR CANCER RESEARCH
(2021)
Article
Cell Biology
Maria Rosaria Dello Stritto, Bernd Bauer, Pierre Barraud, Verena Jantsch
Summary: This study reveals that the depletion of topoisomerase 3 leads to DNA damage in germline cells, reducing the efficiency of apoptosis, which can be alleviated by eliminating certain repair factors. It highlights the crucial role of topoisomerase 3 in ensuring germ cell quality control through regulating DNA repair and apoptosis pathways.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Dalileh Nabi, Hauke Drechsler, Johannes Pschirer, Franz Korn, Nadine Schuler, Stefan Diez, Rolf Jessberger, Mariola Chacon
Summary: Chromosome segregation is crucial for preventing aneuploidy in mammalian oocytes, but it becomes less efficient with age. The protein CENP-V plays a significant role in oocyte spindle formation and chromosome segregation, with Cenp-V-/- oocytes showing age-related weakening of the spindle assembly checkpoint.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Lei Wang, Thomas Kruse, Blanca Lopez-Mendez, Yuqing Zhang, Chunlin Song, Lei Zhu, Bing Li, Jing Fang, Zhimin Lu, Jakob Nilsson, Gang Zhang
Summary: The Bub1 and BubR1 kinetochore proteins are involved in chromosome segregation and the mitotic checkpoint. While Bub1 is a kinase, BubR1 localizes a phosphatase to kinetochores in humans. This study shows that integrating kinase and phosphatase activities within the Bub complex is necessary for maintaining proper mitotic progression.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Developmental Biology
Carolina Zapater i Morales, Peter J. Carman, David B. Soffar, Stefanie E. Windner, Roberto Dominguez, Mary K. Baylies
Summary: Proper muscle contraction requires the assembly and maintenance of sarcomeres and myofibrils. Here, we show that knockdown of Drosophila Tropomodulin (Tmod) results in various myopathy-related phenotypes, including reduction in muscle cell size, disorganization of myofibrils, and accumulation of F-actin. Our findings provide significant insights into the role of Tmod in muscle development, maintenance, and disease.
Article
Cell Biology
Timothy B. Branigan, David Kozono, Amy E. Schade, Peter Deraska, Hembly G. Rivas, Larissa Sambel, Hunter D. Reavis, Geoffrey Shapiro, Alan D. D'Andrea, James A. DeCaprio
Summary: This study identified that knockout of MMB-FOXM1 complex components LIN54 and FOXM1 reduced CHK1 inhibitor-induced DNA replication stress markers and premature mitosis during Late S phase. Activation of a feedback loop between the MMB-FOXM1 complex and CDK1 is required for CHK1 inhibitor-induced premature mitosis in Late S phase and subsequent replication catastrophe. These findings offer mechanistic insights into small molecule inhibitors under clinical trials and support combination therapies.
Article
Multidisciplinary Sciences
D. Cruz-Zarate, O. Lopez-Ortega, D. A. Giron-Perez, A. M. Gonzalez-Suarez, J. L. Garcia-Cordero, M. Schnoor, L. Santos-Argumedo
Summary: Myosin-1g deficiency affects the migration of B lymphocytes, reducing their ability to enter lymph nodes. Lack of Myo1g causes adhesion and chemotaxis defects, as well as flaws in adopting a migratory morphology.
SCIENTIFIC REPORTS
(2021)
Article
Plant Sciences
Naoki Takata, Taku Tsuyama, Soichiro Nagano, Kei'ichi Baba, Yuko Yasuda, Shingo Sakamoto, Nobutaka Mitsuda, Toru Taniguchi
Summary: The study found that wood fiber cells lacking SCWs in aspen trees had thinner SCWs or even no SCW, while cells with SCWs formed G-layers. Mutants showed growth eccentricity and posture control deficiencies when grown on an incline, indicating the essential role of SCWs in G-layer formation and posture control.
Article
Cell & Tissue Engineering
Zheng Wang, Dongdong Wei, Ennan Bin, Jiao Li, Kewu Jiang, Tingting Lv, Xiaoxu Mao, Fengchao Wang, Huaping Dai, Nan Tang
Summary: Impaired differentiation of alveolar stem cells in lung diseases has been investigated in this study, focusing on understanding the impact of aging on alveolar regeneration. The study reveals that the process of alveolar type II (AT2) cells differentiating into AT1 cells is energetically costly and is supported by activated AMPK-PFKFB2 signaling and glycolysis. Aging results in reduced AMPK-PFKFB2 signaling and ATP production in AT2 cells, leading to impaired alveolar regeneration. However, activating AMPK-PFKFB2 signaling can rescue the defective regeneration in aged mice, suggesting that modulating this pathway promotes alveolar repair in aging lungs.
Article
Multidisciplinary Sciences
Didier Boucher, Ruvini Kariawasam, Joshua Burgess, Adrian Gimenez, Tristan E. Ocampo, Blake Ferguson, Ali Naqi, Graeme J. Walker, Emma Bolderson, Roland Gamsjaeger, Kenneth J. O'Byrne, Liza Cubeddu, Kum Kum Khanna, Derek J. Richard
Summary: This study identified the critical role of human Single-Stranded DNA Binding protein 2 (hSSB2) in cellular response to UV exposure, including its rapid chromatin binding, impact on Replication Protein A (RPA32) phosphorylation, delayed recruitment of Xeroderma Pigmentosum group C (XPC), and increased cellular sensitivity to UVB. Moreover, hSSB2 was found to have affinity for single-strand DNA with CPD and duplex DNA mimicking a CPD moiety, demonstrating its involvement in DNA damage repair mechanisms in response to UV exposure.
SCIENTIFIC REPORTS
(2021)
Article
Engineering, Biomedical
Young Kim, Le Thi Hong Tram, Kyung Ah Kim, Byoung Choul Kim
Summary: Cancer metastasis is influenced by chemical factors and physical cues, particularly mechanical tension of integrins and physical confinement. A microconfinement tension gauge platform is developed to monitor spatial integrin tension in metastatic breast cancer cells. The results reveal that the cells exert the strongest integrin tension at the leading edges during migration on a planar surface, while the tension increases at the cell rear when entering microconfinement. The findings identify the mechanical interactions between integrin tension and microenvironment as a key mechanism for cancer invasion and metastasis.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Cell Biology
Arnaud Rondelet, Yu-Chih Lin, Divya Singh, Arthur T. Porfetye, Harish C. Thakurle, Andreas Hecker, Pia Brinket, Nadine Schmidt, Shweta Bendre, Franziska Mueller, Lisa Mazul, Per O. Widlund, Tanja Bange, Michael Hiller, Ingrid R. Vetter, Alexander W. Bird
JOURNAL OF CELL BIOLOGY
(2020)
Article
Cell Biology
Kimberly K. Fong, Trisha N. Davis, Charles L. Asbury
Summary: To assemble a bipolar spindle, microtubules need to bundle into an antiparallel midzone, which can be achieved by overcoming the initial preference for parallel interactions through pivoting. Pivoting flexibility of microtubules around spindle poles is crucial for timely pole separation, with passive thermal pivoting aiding initial contact and active minus end-directed force generation required for antiparallel alignment.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Microbiology
Daniel E. Velez-Ramirez, Michelle M. Shimogawa, Sunayan S. Ray, Andrew Lopez, Shima Rayatpisheh, Gerasimos Langousis, Marcus Gallagher-Jones, Samuel Dean, James A. Wohlschlegel, Kent L. Hill
Summary: Trypanosoma brucei is the protozoan parasite responsible for sleeping sickness, and its flagellum plays critical roles in transmission and pathogenesis. APEX2-based proximity proteomics has been successfully used to examine the protein composition of T. brucei flagellum subdomains, allowing for the identification of unique proteomes for different regions of the flagellum.
Article
Biology
Axel F. Brilot, Andrew S. Lyon, Alex Zelter, Shruthi Viswanath, Alison Maxwell, Michael J. MacCoss, Eric G. Muller, Andrej Sali, Trisha N. Davis, David A. Agard
Summary: This study investigates the mechanisms of γ TuRC assembly using a combination of crosslinking mass spectrometry, X-ray crystallography, and cryo-EM structures. The results highlight the crucial role of the evolutionarily conserved CM1 motif in Spc110p in aiding γ TuRC assembly, showing that phosphorylation sites are mostly inhibitory. Comparison with the human γ TuRC structure reveals significant structural changes arising from CM1 helix binding in metazoan γ TuRC.
Article
Cell Biology
Katharina S. Keuenhof, Lisa Larsson Berglund, Sandra Malmgren Hill, Kara L. Schneider, Per O. Widlund, Thomas Nystrom, Johanna L. Hoog
Summary: This study reveals the restructuring of the internal architecture of cells during progressive heat shock, including changes in organelle numbers, sizes, and morphologies. Different organelles respond to heat shock at different times, and adaptive changes in the morphology of specific organelles were observed.
JOURNAL OF CELL SCIENCE
(2022)
Article
Chemistry, Analytical
Michael Riffle, Michael R. Hoopmann, Daniel Jaschob, Guo Zhong, Robert L. Moritz, Michael J. MacCoss, Trisha N. Davis, Nina Isoherranen, Alex Zelter
Summary: The study introduces Magnum and Limelight, an algorithm and software package for the identification and visualization of xenobiotic-protein adducts. Through validation and application, the methods and software enable accurate identification of xenobiotic-protein adducts and fill the gap in comprehensive data visualization tools in the field of open-mass searching.
ANALYTICAL CHEMISTRY
(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)
Biographical-Item
Multidisciplinary Sciences
John D. Scott, Trisha N. Davis, Rachel E. Klevit, William A. Catterall
Article
Cell Biology
Rachel L. Flores, Zachary E. Peterson, Alex Zelter, Michael Riffle, Charles L. Asbury, Trisha N. Davis
Summary: The study reveals that interactions between Ndc80 complex and Dam1 complex through three distinct interacting regions play a vital role in supporting both short-term and long-term tip-coupling during mitosis. Phosphorylation by Aurora B kinase may modulate these interactions and impact the accuracy of mitosis.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katherine H. Reiter, Alex Zelter, Maria K. Janowska, Michael Riffle, Nicholas Shulman, Brendan X. MacLean, Kaipo Tamura, Matthew C. Chambers, Michael J. MacCoss, Trisha N. Davis, Miklos Guttman, Peter S. Brzovic, Rachel E. Klevit
Summary: This study characterized the interaction between the auto-inhibited RBR ligase HHARI and its substrate 4EHP using a combination of techniques. The results revealed a binding platform on the catalytic domain of HHARI and the role of a phosphomimetic mutation in promoting the release and reorientation of Rcat for substrate modification. These findings identify a direct binding interaction between an RBR ligase and its substrate and propose a general model for substrate recognition.
Article
Biochemistry & Molecular Biology
Kara L. Schneider, Doryaneh Ahmadpour, Katharina S. Keuenhof, Anna Maria Eisele-Burger, Lisa Larsson Berglund, Frederik Eisele, Roja Babazadeh, Johanna L. Hoog, Thomas Nystrom, Per O. Widlund
Summary: The accumulation of misfolded proteins is a common feature of aging and neurodegenerative diseases. This study compares the handling of three different misfolded proteins by cells and finds significant differences in their aggregation and disaggregation behavior. The results suggest that the properties of misfolded proteins can significantly affect their processing.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Michael R. Hoopmann, David D. Shteynberg, Alex Zelter, Michael Riffle, Andrew S. Lyon, David A. Agard, Qing Luan, Brad J. Nolen, Michael J. MacCoss, Trisha N. Davis, Robert L. Moritz
Summary: Fragmentation ion spectral analysis is an established technology for determining protein interactions, spatial orientation, and structure. Kojak version 2.0 is a major update to the original algorithm, with improved scoring metrics and support for cleavable cross-linkers. It is now integrated into the Trans-Proteomic Pipeline, enhancing its versatility and accuracy in cross-link identification.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Michelle M. Shimogawa, Angeline S. Wijono, Hui Wang, Jiayan Zhang, Jihui Sha, Natasha Szombathy, Sabeeca Vadakkan, Paula Pelayo, Keya Jonnalagadda, James Wohlschlegel, Z. Hong Zhou, Kent L. Hill
Summary: In this study, researchers identified a crucial microtubule inner protein (MIP) FAP106 in the pathogenic protozoan Trypanosoma brucei that regulates the motility of the parasite by directing the assembly of other MIPs. They also discovered a trypanosome-specific MIP, MC8, that is essential for parasite motility. These findings enhance our understanding of MIP assembly mechanisms and provide potential targets for therapeutic intervention.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Biophysics
Rachel L. Flores, Zachary Peterson, Charles L. Asbury, Trisha Davis
BIOPHYSICAL JOURNAL
(2021)