Review
Biochemistry & Molecular Biology
Alexandra G. Liddane, James M. Holaska
Summary: It is commonly recognized in the field that cancer cells exhibit changes in the size and shape of their nuclei, which can impact cell migration and metastasis. Nuclear structural changes are predicted to regulate cancer cell migration across various tumor types, and alterations in nuclear lamina proteins, such as emerin, may play a significant role in cancer progression and clinical outcomes. Understanding the factors driving these nuclear abnormalities and their functional consequences remains an area of ongoing research in the field of cancer biology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Natalie Y. Chen, Paul H. Kim, Yiping Tu, Ye Yang, Patrick J. Heizer, Stephen G. Young, Loren G. Fong
Summary: The expression level of LAP2I3 is negatively correlated with the frequency of nuclear membrane ruptures in cells deficient in nuclear lamins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Catia Silva Janota, Andreia Pinto, Anna Pezzarossa, Pedro Machado, Judite Costa, Pedro Campinho, Claudio A. Franco, Edgar R. Gomes
Summary: The endoplasmic reticulum shields immobile ventral stress fibers to establish asymmetric nucleo-cytoskeleton connections with moving dorsal actin cables for nuclear positioning.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Gary S. Coombs, Jose L. Rios-Monterrosa, Shuping Lai, Qiang Dai, Ashley C. Goll, Margaret R. Ketterer, Maria F. Valdes, Nnamdi Uche, Ivor J. Benjamin, Lori L. Wallrath
Summary: In this study, researchers used new Drosophila models and human iPS cell-derived cardiomyocytes to investigate the mechanisms of muscle diseases caused by LMNA gene mutations. They found that mutant lamins caused nuclear envelope defects, activation of the Nrf2/Keap1 redox pathway, and reductive stress. Potential therapeutic targets were identified through genetic and pharmacological interventions in the Drosophila models. The models provided insights for the development of treatments for LMNA-associated muscular dystrophy.
Review
Immunology
Anna Selezneva, Alasdair J. Gibb, Dean Willis
Summary: The traditional view of the nuclear envelope as an inert physical barrier has been challenged by recent research, which suggests that it plays important roles in regulating cellular functions, particularly in immune cells. The nuclear envelope may serve as a sensor/transducer of mechanical signals and an integrator of mechanical and chemical signals, allowing precise regulation of gene transcription and functionality in immune cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
A. K. Balaji, Santam Saha, Shruti Deshpande, Darshini Poola, Kundan Sengupta
Summary: Dysregulation of chromatin remodeling and nuclear envelope proteins plays a significant role in cancer development. Recent advances in single-cell sequencing, imaging technologies, and data mining approaches enable the design of small molecules to selectively inhibit cancer cell growth and proliferation in a genome- and epigenome-specific manner.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biophysics
Parsa Zareiesfandabadi, Mary Williard Elting
Summary: The mitotic spindle plays a critical role in chromosome segregation during cell division. Through laser ablation experiments, the collapse of the spindle was found to require microtubule dynamics and specific motor proteins.
BIOPHYSICAL JOURNAL
(2022)
Article
Cell Biology
Mark C. Field
Summary: The nucleus is highly conserved, but there are significant compositional divergences within nuclear structures among different eukaryotic lineages, reflecting adaptations and distinct mechanisms. These studies highlight the malleability of nuclear architecture and call for further exploration of nuclear function in non-canonical experimental organisms.
CURRENT OPINION IN CELL BIOLOGY
(2023)
Review
Plant Sciences
Gilles Dupouy, Yihan Dong, Etienne Herzog, Marie-Edith Chaboute, Alexandre Berr
Summary: The nucleus is a central organelle in eukaryotic cells that undergoes dynamic structural changes during cellular processes. This review focuses on recent data obtained in plants, particularly in response to mechanical stress, and highlights the similarities and differences between animal and plant cells in terms of nuclear envelope dynamics and functional impacts.
Article
Cell Biology
Maria Chatzifrangkeskou, Caroline Le Dour, Antoine Muchir
Summary: Dilated cardiomyopathy caused by LMNA mutations is a common cause of sudden death and heart failure. A-type lamins play a crucial role in maintaining nuclear structure and organizing the cytoskeleton. LMNA mutations can disrupt various structural components and cytoskeletal proteins, leading to poor cardiac contractility. Targeting cytoskeletal dynamics could be a potential therapeutic approach for LMNA cardiomyopathy.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Emily S. Bell, Pragya Shah, Noam Zuela-Sopilniak, Dongsung Kim, Alice-Anais Varlet, Julien L. P. Morival, Alexandra L. McGregor, Philipp Isermann, Patricia M. Davidson, Joshua J. Elacqua, Jonathan N. Lakins, Linda Vahdat, Valerie M. Weaver, Marcus B. Smolka, Paul N. Span, Jan Lammerding
Summary: Lower expression of nuclear envelope protein lamin A/C in breast cancer cells leads to increased nuclear deformability and enhanced cell migration. Lamin A/C expression also affects pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Lower lamin A levels in breast tumors are associated with Akt signaling activation and decreased disease-free survival.
Article
Microbiology
Jing Xu, Jie Gao, Maolin Zhang, Danwei Zhang, Ming Duan, Zhenhong Guan, Yidi Guo
Summary: Rabies virus infects N2a cells in a manner dependent on microtubule integrity as well as the function of dynein and kinesin. Microtubule-depolymerizing drugs, dynein inhibitors, and disruption of kinesin function can all hinder Rabies virus infection.
VETERINARY MICROBIOLOGY
(2021)
Article
Biology
Andrea Fracchia, Gabi Gerlitz
Summary: The connection between the metazoan nucleus and the actin cytoskeleton is crucial for various cellular processes and can influence cancer development. Different mechanisms have been identified to explain the organization of actin filaments next to the nucleus.
Article
Biochemistry & Molecular Biology
Patrick Feurle, Andreas Abentung, Isabella Cera, Nico Wahl, Cornelia Ablinger, Michael Bucher, Eduard Stefan, Simon Sprenger, David Teis, Andre Fischer, Aodan Laighneach, Laura Whitton, Derek W. Morris, Galina Apostolova, Georg Dechant
Summary: Interactions between SATB2 and the inner nuclear membrane protein LEMD2 influence gene expression programs in pyramidal neurons that are linked to cognitive ability and psychiatric disorder etiology.
Article
Biochemistry & Molecular Biology
Benjamin E. Hinz, Sydney G. Walker, Austin Xiong, Rose A. Gogal, Michael J. Schnieders, Lori L. Wallrath
Summary: Mutations in the LMNA gene cause laminopathies, with different amino acid substitutions leading to distinct diseases in Lamin A/C. The nature of the amino acid replacement may dictate disease severity and pathogenicity. In silico analyses suggest potential genotype-phenotype connections in laminopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Orly Reiner, Arpan Parichha, Tamar Sapir
Summary: Advancements in understanding human neuronal migration disorders using mouse models have been significant, despite the notable differences between human and mouse genetic information and developmental processes. The development of human brain organoid models has sparked excitement in modeling human neuronal migration diseases. Differences in gene expression, morphology, and migratory routes between human and mouse brains highlight the need for further study.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Arpan Parichha, Varun Suresh, Mallika Chatterjee, Aditya Kshirsagar, Lihi Ben-Reuven, Tsviya Olender, M. Mark Taketo, Velena Radosevic, Mihaela Bobic-Rasonja, Sara Trnski, Michael J. Holtzman, Natasa Jovanov-Milosevic, Orly Reiner, Shubha Tole
Summary: The choroid plexus, responsible for secreting cerebrospinal fluid, plays a critical role in brain development and function. Activation of the Wnt signaling pathway is essential for the proper development of the choroid plexus, but over-activation of this pathway can lead to a loss of its properties and transformation into neurons.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lukasz Stanislaw Kaczmarczyk, Nehora Levi, Tamar Segal, Mali Salmon-Divon, Gabi Gerlitz
Summary: More than one third of the mammalian genome is associated with the nuclear lamina, called lamina-associated domains (LADs), which play a fundamental role in chromatin biology. LADs association with the nuclear envelope relies on the interaction between nuclear membrane proteins and heterochromatin modifications, as well as proteins that bind the borders of LADs. CTCF is identified as a key factor in assisting the association of facultative, short LADs with the nuclear lamina upon chromatin stress.
CHROMOSOME RESEARCH
(2022)
Review
Cell Biology
Tamar Sapir, Dalit Sela-Donenfeld, Maayan Karlinski, Orly Reiner
Summary: This passage discusses the development and organization of the cortex from the caudal regions of the segmented neural tube, and suggests using a developmental perspective to understand common cortical malformations and their manifestation in the human brain.
Article
Cell Biology
E. Dominguez-Sala, L. Valdes-Sanchez, S. Canals, O. Reiner, A. Pombero, R. Garcia-Lopez, A. Estirado, D. Pastor, E. Geijo-Barrientos, S. Martinez
Summary: LIS1 (PAFAH1B1) plays a major role in the developing cerebral cortex and mutations in this gene can cause lissencephaly type 1. Research on mutant mice with a deletion in the first exon of the Lis1 gene revealed abnormal distribution and functional abnormalities in cortical GABAergic interneurons. Additionally, these mice exhibited altered oscillatory activity and abnormalities in the fast spiking inhibitory GABAergic interneurons. These findings suggest that certain mutations in the Lis1 gene can lead to phenotypes similar to those observed in patients with schizophrenia and autism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tamar Sapir, Aditya Kshirsagar, Anna Gorelik, Tsviya Olender, Ziv Porat, Ingrid E. Scheffer, David B. Goldstein, Orrin Devinsky, Orly Reiner
Summary: HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with a higher sensitivity of the latter. The expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu's conditional truncation. Pharmaceutical and genetic agents have been identified to partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Sergiu P. Pasca, Paola Arlotta, Helen S. Bateup, J. Gray Camp, Silvia Cappello, Fred H. Gage, Juergen A. Knoblich, Arnold R. Kriegstein, Madeline A. Lancaster, Guo-Li Ming, Alysson R. Muotri, In-Hyun Park, Orly Reiner, Hongjun Song, Lorenz Studer, Sally Temple, Giuseppe Testa, Barbara Treutlein, Flora M. Vaccarino
Summary: The nomenclature of human multicellular models of nervous system development and disease, including organoids, assembloids, and transplants, is clarified and provided as a basic framework to facilitate progress and improve communication with the scientific community and the public. These models derived from human pluripotent stem cells or primary tissue have the potential to provide insights into the unique development of the human nervous system and the progression and treatment of nervous system disorders.
Article
Cell Biology
Rosari Hernandez-Vicens, Jagreeti Singh, Nomi Pernicone, Tamar Listovsky, Gabi Gerlitz
Summary: Our study suggests that SETDB1 affects microtubule dynamics by interacting with both microtubules and HDAC6 to enhance tubulin deacetylation. These findings provide a novel insight into the cytoplasmic role of SETDB1 in the regulation of microtubule dynamics.
CELL PROLIFERATION
(2022)
Editorial Material
Neurosciences
Liang Qiang, Michael A. Lane, Claudia A. Doege, Orly Reiner, Itzhak Fischer
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Andrew K. Ressler, Gabriela L. A. Sampaio, Sarah A. Dugger, Tamar Sapir, Daniel Krizay, Michael J. Boland, Orly Reiner, David B. Goldstein
Summary: Generating effective therapies for neurodevelopmental disorders is challenging. An emerging approach is to characterize transcriptomic dysregulation in a model system and screen for therapeutics that restore functional expression patterns. We characterized dysregulation in a human model of HNRNPU-related disorder and compared it to mice models, finding enrichment of co-dysregulation between human organoids and embryonic mice. However, hnRNPU-deficient human organoids may only model transcriptional dysregulation in certain cell types during specific developmental periods.
Article
Biochemistry & Molecular Biology
Santosh Kumar, Valid Gahramanov, Shivani Patel, Julia Yaglom, Lukasz Kaczmarczyk, Ivan A. Alexandrov, Gabi Gerlitz, Mali Salmon-Divon, Michael Y. Sherman
Summary: Resistance to chemotherapy is commonly caused by mutations or changes in protein expression. The selection of drug-resistant mutants can occur randomly prior to treatment or through the generation of mutations during treatment. Here, we studied the origin of resistance mutations to the Top1 inhibitor irinotecan and found that the mutations accumulated in non-coding regions of DNA at Top1-cleavage sites. Cancer cells had a higher number of these sites compared to the reference genome, contributing to their increased sensitivity to irinotecan. These mutations gradually reduced the generation of DNA breaks and increased drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Tamar Sapir, Orly Reiner
Summary: Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a nuclear protein that is involved in important biological functions such as RNA splicing and chromatin organization. Its activities, along with scaffold attachment factor A (SAF-A), are crucial for various processes including gene expression, DNA replication, genome integrity, and mitotic fidelity. HNRNPU is associated with neurodevelopmental disorders characterized by developmental delay and intellectual disability. Our research shows that the loss of HNRNPU function results in the death of neural progenitor cells and post-mitotic neurons, affecting gene expression and alternative splicing of genes involved in signaling pathways related to HNRNPU-related neurodevelopmental disorders.
Article
Biochemistry & Molecular Biology
Katherine Chiu, Yasmin Berrada, Nebiyat Eskndir, Dasol Song, Claire Fong, Sarah Naughton, Tina Chen, Savanna Moy, Sarah Gyurmey, Liam James, Chimere Ezeiruaku, Caroline Capistran, Daniel Lowey, Vedang Diwanji, Samantha Peterson, Harshini Parakh, Ayanna R. Burgess, Cassandra Probert, Annie Zhu, Bryn Anderson, Nehora Levi, Gabi Gerlitz, Mary C. Packard, Katherine A. Dorfman, Michael Seifu Bahiru, Andrew D. Stephens
Summary: Mitosis is a crucial process that ensures equal segregation of duplicated genome into two daughter cells. Recent studies have shown that CTCF plays an important role in mitosis by localizing CENP-E. In this study, using CRISPR-based genetic knockdowns, the researchers examined the impact of CTCF on mitotic fidelity. They found that CTCF knockdown resulted in prolonged mitoses and failed anaphase segregation. The knockdown also led to abnormal mitotic spindle organization and increased nuclear size. These findings highlight the significance of CTCF in both metaphase organization and anaphase segregation during mitosis.
Article
Medicine, Research & Experimental
Manuela Cassotta, Hugo Geerts, Lise Harbom, Tiago F. Outeiro, Iosif Pediaditakis, Orly Reiner, Stefan Schildknecht, Jens C. Schwamborn, Jarrod Bailey, Kathrin Herrmann, Helena T. Hogberg
Summary: Parkinson's disease (PD) is a complex neurodegenerative condition with a lack of preventive or curative therapies. New approach methodologies (NAMs) hold potential to advance PD research and reduce the reliance on animal-based studies. Key recommendations to advance PD research include integrating NAMs, learning from other neurodegenerative diseases, increasing data sharing, promoting innovative pilot studies, and accessing philanthropic funding.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Meeting Abstract
Biophysics
Orly Reiner, Aditya Kshirsagar
BIOPHYSICAL JOURNAL
(2022)