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Volume 122 of Methods in Cell Biology describes modern tools and techniques used to study nuclear pore complexes and nucleocytoplasmic transport in diverse eukaryotic model systems (including mammalian cells, Xenopus, C. elegans, yeast). The volume enables investigators to analyze nuclear pore complex structure, assembly, and dynamics; to evaluate protein and RNA trafficking through the nuclear envelope; and to design in vivo or in vitro assays appropriate to their research needs. Beyond the study of nuclear pores and transport as such, these protocols will also be helpful to scientists characterizing gene regulation, signal transduction, cell cycle, viral infections, or aging. The NPC being one of the largest multiprotein complexes in the cell, some protocols will also be of interest for people currently characterizing other macromolecular assemblies. This book is thus designed for laboratory use by graduate students, technicians, and researchers in many molecular and cellular disciplines. - Describes modern tools and techniques used to study nuclear pore complexes and nucleocytoplasmic transport in diverse eukaryotic model systems (mammalian cells, Xenopus, C. elegans, yeast) - Chapters are written by experts in the field - Cutting-edge material
Dysfunction of nuclear-cytoplasmic transport systems has been associated with many human diseases. Thus, understanding of how functional this transport system maintains, or through dysfunction fails to maintain remains the core question in cell biology. In eukaryotic cells, the nuclear envelope (NE) separates the genetic transcription in the nucleus from the translational machinery in the cytoplasm. Thousands of nuclear pore complexes (NPCs) embedded on the NE selectively mediate the bidirectional trafficking of macromolecules such as RNAs and proteins between these two cellular compartments. In this book, the authors integrate recent progress on the structure of NPC and the mechanism of nuclear-cytoplasmic transport system in vitro and in vivo.
In eukaryotic cells, the nuclear genome and its transcriptional apparatus is separated from the site of protein synthesis by the nuclear envelope. Thus, a constant flow of proteins and nucleic acids has to cross the nuclear envelope in both directions. This transport in and out of the nucleus is mediated by nuclear pore complexes (NPCs) and occurs in an energy and signal-dependent manner. Thus, nucleocytoplasmic translocation of macro molecules across the nuclear envelope appears to be a highly specific and regulated process. Viruses that replicate their genome in the cell nucleus are therefore forced to develop efficient ways to deal with the intracellulZlr host cell transport machinery. Historically, investigation of Polyomavirus replication allowed identification ofsequences that mediate nuclear import, which led subsequently to our detailed understanding of the cellular factors that are involved in nuclear import. Transport ofmacromolecules in the opposite direction, however, is less well understood. The investigation of retroviral gene expression in recent years pro vided the first insights into the cellular mechanisms that regulate nuclear export. In particular, the detailed dissection of the function of the human immunodeficiency virus type I (HIV-I) Rev trans-activator protein identified CRMI, as a hona fide nuclear export receptor. CRM I appears to be involved in the nucleocytoplasmic translocation of the vast majority of viral and cellular proteins that have subsequently been found to contain a Rev-type leucine-rich nuclear export signal (NES).
Bidirectional traffic of macromolecules across the nuclear envelope is an active and essential transport process in all eukaryotic cells. Work on various model systems has led to a tremendous increase in our understanding of nuclear transport in recent years. This volume summarizes our current knowledge of protein and RNA transport into and out of the nucleus. It contains nine up-to-date reviews which cover various aspects of nucleocytoplasmic transport, including the structure and function of the nuclear pore complex, the role of soluble transport factors in protein and RNA transport, and the regulation of protein transport through the nuclear pore.
Nuclear Import and Export in Plants and Animals provides insight into the remarkable mechanisms of nuclear import and export. This book covers a range of topics from the nuclear pore structure, to nuclear import and export of macromolecules in plant and animal cells. In addition, the book covers the special cases of nuclear import of Agrobacterium T-DNA during plant genetic transformation, nuclear import and export of animal viruses, and nuclear intake of foreign DNA. A chapter on research methods to study nuclear transport concludes the book.
Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.
"Nuclear envelope (NE) defects have been linked to cancer biology since the mid-1800s, but it was not until the last few years that we have begun to understand these historical links and to realize that there are myriad ways that the NE impacts on tumorigenesis. The NE is a complex double membrane system that encloses the genome while providing structural support through the intermediate filament lamin polymer and regulating protein/ mRNA trafficking and signaling between the nucleus and cytoplasm via the nuclear pore complexes (NPCs). These functions already provide some mechanisms for NE influences on cancer biology but work in the past few years has elucidated many others. Lamins and many recently identified NE transmembrane proteins (NETs) have been now shown to function in DNA repair, regulation of cell cycle and signaling, apoptosis, cell migration in metastasis and nuclear architecture and morphology. This volume presents a comprehensive overview of the wide range of functions recently identified for NE proteins and their relevance in cancer biology, providing molecular mechanisms and evidence of their value as prognostic and diagnostic markers and suggesting new avenues for the treatment of cancer. Indeed some of these recent links are already yielding promising therapies, such as the current clinical trial of selective inhibitors of the nuclear export factor exportin in certain types of leukemia, melanoma and kidney cancer."
It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre--‐mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--‐ coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi--‐directional transcription and production of repeat associated non--‐ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer’s disease, Huntington’s disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways.
Pharmacoepigenetics provides a comprehensive volume on the role of epigenetics and epigenomics in drug discovery and development, providing a detailed, but accessible, view of the field, from basic principles, to applications in disease therapeutics. Leading international researchers from across academia, clinical settings and the pharmaceutical industry discuss the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, and treatment, current epigenetic drugs, and the application of epigenetic procedures in drug development. Throughout the book, chapter authors offer a balanced and objective discussion of the future of pharmacoepigenetics and its crucial contribution to the growth of precision and personalized medicine. - Fully examines the influence of epigenetics and epigenomics in human pathology, epigenetic biomarkers for disease prediction, diagnosis, treatment, current epigenetic drugs and the application of epigenetic procedures in drug development - Features chapter contributions from leading international researchers in academia, clinical settings and the pharmaceutical industry - Instructs researchers, students and clinicians on how to better interpret and employ pharmacoepigenetics in drug development, efficiency and safety - Provides a balanced and objective discussion of the future of pharmacoepigenetics and its crucial role in precision medicine
Nuclear Architecture and Dynamics provides a definitive resource for (bio)physicists and molecular and cellular biologists whose research involves an understanding of the organization of the genome and the mechanisms of its proper reading, maintenance, and replication by the cell. This book brings together the biochemical and physical characteristics of genome organization, providing a relevant framework in which to interpret the control of gene expression and cell differentiation. It includes work from a group of international experts, including biologists, physicists, mathematicians, and bioinformaticians who have come together for a comprehensive presentation of the current developments in the nuclear dynamics and architecture field. The book provides the uninitiated with an entry point to a highly dynamic, but complex issue, and the expert with an opportunity to have a fresh look at the viewpoints advocated by researchers from different disciplines. - Highlights the link between the (bio)chemistry and the (bio)physics of chromatin - Deciphers the complex interplay between numerous biochemical factors at task in the nucleus and the physical state of chromatin - Provides a collective view of the field by a large, diverse group of authors with both physics and biology backgrounds