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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.
The means by which proteins and RNAs are exchanged between cytoplasm and nucleus have interested cell biologists for many years, and the field has seen a number of exciting recent advances. Much has been learned about the intricate architecture of the nuclear pore-complex, the mechanisms by which transport substrates are sorted, and the supply of energy for exchange processes. This book attempts a general review of the growing body of knowledge. However, the authors challenge the presumptions implicit in some interpretations of the evidence, re-examining the concept of "transport" within cells, and suggesting that lessons learned from nucleocytoplasmic transport studies can elucidate wider aspects of cell biology.
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.
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
Delivery of therapeutic proteomics and genomics represent an important area of drug delivery research. Genomics and proteomics approaches could be used to direct drug development processes by unearthing pathways involved in disease pathogenesis where intervention may be most successful. This book describes the basics of genomics and proteomics and highlights the various chemical, physical and biological approaches to protein and gene delivery. Covers a diverse array of topics from basic sciences to therapeutic applications of proteomics and genomics delivery Of interest to researchers in both academia and industry Highlights what’s currently known and where further research is needed
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.