The Non-canonical Role of Autophagy Components in the Secretion of Neural Peptide Hormones PDF Download
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Category : Electronic books
Languages : en
Pages : 47
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Book Description
The canonical autophagy pathway has primarily been described as a degradative mechanism, which clears the cell of old damaged organelles, protein aggregates and pathogens. Central to the pathway is the de novo formation of a vesicle structure called the autophagosome, which fuses with lysosomes to degrade its content. The Atg8a/MAP1-LC3 protein family is essential for the formation of the autophagosome, and Atg8a mutations result in a variety of defects related to decreased autophagic function. Recently, we have observed a phenotype in Atg8a mutant Drosophila that is consistent with secretory defects of the peptide hormone Bursicon, which is responsible for wing expansion and cuticle hardening upon eclosion. This observation is in accordance with other recent findings which show that components of the autophagy pathway are also involved in the secretion of bioactive molecules. However, the intersection of autophagy and secretory pathways is not yet fully understood. Here, we show that along with Bursicon two additional peptide hormones are differentially secreted and show impaired hemolymph profiles when autophagic function is lowered in the fly nervous system. This includes the release of the pigment dispersing factor (PDF, circadian cycle) and the mesencephalic astrocyte-derived neurotrophic factor (dMANF, stress response), which is highlighted by the aberrant sleep-circadian behaviors (PDF) and trauma-mediated sensitivity (MANF) associated with Atg8a1 mutant flies. Based on the Bursicon wing phenotype, we conducted a secretion-based screen using the GAL4/UAS-dsRNAi knockdown system and identified Atg8a and other autophagy components involved with organelle initiation and membrane expansion that show impaired Bursicon release upon knockdown. Furthermore, this did not include genes involved with selective autophagy (aggrephagy) or endosomal-lysosomal trafficking. Findings from this research will have broad implications toward understanding complex secretory defects and the intersection of autophagy with other vesicle trafficking pathways.
Author:
Publisher:
ISBN:
Category : Electronic books
Languages : en
Pages : 47
Get Book Here
Book Description
The canonical autophagy pathway has primarily been described as a degradative mechanism, which clears the cell of old damaged organelles, protein aggregates and pathogens. Central to the pathway is the de novo formation of a vesicle structure called the autophagosome, which fuses with lysosomes to degrade its content. The Atg8a/MAP1-LC3 protein family is essential for the formation of the autophagosome, and Atg8a mutations result in a variety of defects related to decreased autophagic function. Recently, we have observed a phenotype in Atg8a mutant Drosophila that is consistent with secretory defects of the peptide hormone Bursicon, which is responsible for wing expansion and cuticle hardening upon eclosion. This observation is in accordance with other recent findings which show that components of the autophagy pathway are also involved in the secretion of bioactive molecules. However, the intersection of autophagy and secretory pathways is not yet fully understood. Here, we show that along with Bursicon two additional peptide hormones are differentially secreted and show impaired hemolymph profiles when autophagic function is lowered in the fly nervous system. This includes the release of the pigment dispersing factor (PDF, circadian cycle) and the mesencephalic astrocyte-derived neurotrophic factor (dMANF, stress response), which is highlighted by the aberrant sleep-circadian behaviors (PDF) and trauma-mediated sensitivity (MANF) associated with Atg8a1 mutant flies. Based on the Bursicon wing phenotype, we conducted a secretion-based screen using the GAL4/UAS-dsRNAi knockdown system and identified Atg8a and other autophagy components involved with organelle initiation and membrane expansion that show impaired Bursicon release upon knockdown. Furthermore, this did not include genes involved with selective autophagy (aggrephagy) or endosomal-lysosomal trafficking. Findings from this research will have broad implications toward understanding complex secretory defects and the intersection of autophagy with other vesicle trafficking pathways.
Author: Giulia Petroni
Publisher: Academic Press
ISBN: 0128209119
Category : Science
Languages : en
Pages : 184
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Book Description
Non-canonical Autophagy: Mechanisms and Pathophysiological Implications outlines the differences between ‘canonical’ and ‘non-canonical’ forms of autophagy, highlighting the discoveries concerning the molecular mechanisms underlying these unconventional forms of autophagy and the advancements in pathophysiological features of ‘non-canonical’ autophagy. The book discusses all forms of ‘non-canonical’ autophagy and the complexity of autophagy-dependent cell death. Readers will gain a better understanding of mechanisms underlying ‘non-canonical’ autophagy so that they can interpret the biological effects of autophagy correctly and identify reliable, novel and effective treatment strategies. Presents the most advanced information surrounding the molecular mechanisms underlying non-canonical autophagy Outlines the increasing evidence regarding the involvement of non-canonical autophagy in multiple physiological and pathological processes Discusses the therapeutic potential of autophagy modulators and the obstacles that have limited their development
Author: Jos A.F. Op den Kamp
Publisher: Springer Science & Business Media
ISBN: 3642731848
Category : Science
Languages : en
Pages : 474
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Book Description
Many individual aspects of the dynamics and assembly of biological membranes have been studied in great detail. Cell biological approaches, advanced genetics, biophysics and biochemistry have greatly contributed to an increase in our knowledge in this field.lt is obvious however, that the three major membrane constituents - lipids, proteins and carbohydrates- are studied, in most cases separately and that a coherent overview of the various aspects of membrane biogenesis is not readily available. The NATO Advanced Study Institute on "New Perspectives in the Dynamics of Assembly of Biomembranes" intended to provide such an overview: it was set up to teach students and specialists the achievements obtained in the various research areas and to try and integrate the numerous aspects of membrane assembly into a coherent framework. The articles in here reflect this. Statting with detailed contributions on phospholipid structure, dynamics, organization and biogenesis, an up to date overview of the basic, lipidic backbone of biomembranes is given. Extensive progress is made in the research on membrane protein biosynthesis. In particular the post- and co-translational modification processes of proteins, the mechanisms of protein translocation and the sorting mechanisms which are necessary to direct proteins to their final, intra - or extracellular destination have been characterized in detail. Modern genetic approaches were indispensable in this research area: gene cloning, hybrid protein construction, site directed mutagenesis and sequencing techniques elucidated many functional aspects of specific nucleic acid and amino acid sequences.
Author: Laurence Zitvogel
Publisher: Springer
ISBN: 3319624318
Category : Medical
Languages : en
Pages : 700
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Book Description
In this book, leading experts in cancer immunotherapy join forces to provide a comprehensive guide that sets out the main principles of oncoimmunology and examines the latest advances and their implications for clinical practice, focusing in particular on drugs with FDA/EMA approvals and breakthrough status. The aim is to deliver a landmark educational tool that will serve as the definitive reference for MD and PhD students while also meeting the needs of established researchers and healthcare professionals. Immunotherapy-based approaches are now inducing long-lasting clinical responses across multiple histological types of neoplasia, in previously difficult-to-treat metastatic cancers. The future challenges for oncologists are to understand and exploit the cellular and molecular components of complex immune networks, to optimize combinatorial regimens, to avoid immune-related side effects, and to plan immunomonitoring studies for biomarker discovery. The editors hope that this book will guide future and established health professionals toward the effective application of cancer immunology and immunotherapy and contribute significantly to further progress in the field.
Author: Zahra Zakeri
Publisher:
ISBN:
Category : Science
Languages : en
Pages : 236
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Book Description
Contains papers from a July 1998 conference held at the Queens College Campus of the City University of New York. Papers are arranged in sections on mechanisms and general considerations, programmed (developmental) cell death, and cell death and pathological and clinical situations. Specific topics
Author: Andrej Spec
Publisher: Elsevier Health Sciences
ISBN: 0323568645
Category : Medical
Languages : en
Pages : 942
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Book Description
Perfect for board review or quick reference in clinical practice, Comprehensive Review of Infectious Diseases is a balanced, high-yield resource covering the full range of infectious disease topics. Whether you’re preparing for examinations or are looking for a concise resource to support your practice, this unique review contains precisely the information you need – from common infectious diseases concepts and conditions to hundreds of up-to-date review questions and answers for self-assessment and exam preparation. Covers the most frequently encountered concepts and conditions in infectious diseases. Covers challenging areas frequently covered on the boards: clinically-relevant microbiology and ID pharmacology, HIV and antiretroviral therapy, infections in immunocompromised hosts, dermatologic manifestations of ID, infection mimics, infection control and prevention, and more. Includes new and emerging topics such as neglected tropical diseases, bioterrorism, and emerging and re-emerging infections. Provides more than 550 case-based, board-style multiple-choice questions and answers for test prep and self-assessment. Facilitates quick review and maximum retention of information by including hundreds of high-quality illustrations, tables, high-yield boxes, and bulleted lists. Contains practical tips for taking the boards, buzzwords and memory aids for board questions, and clinical and board pearls. Edited and written by rising stars in the field of infectious diseases – authors who have recently taken the boards and excelled, and who understand the challenges posed by this complex field of study and practice.
Author: Frederick R. Maxfield
Publisher: John Wiley & Sons
ISBN: 1118978315
Category : Medical
Languages : en
Pages : 586
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Book Description
Discussing recent findings, up-to-date research, and novel strategies, the book integrates perspectives from pharmacology, toxicology, and biochemistry to illustrate the potential of lysosomes in drug discovery and development. • Explores basic principles and properties of lysosomes that allow them to act as regulators of cell metabolism, therapeutic targets, and sites for activation of drug conjugates • Discusses the role of lysosomes in metabolism, drug targeting, apoptosis, cancer, aging, inflammation, autophagy, metabolism, toxicity, and membrane repair • Introduces new pathways in therapeutic development and new mechanisms in drug development
Author: Hans-Joachim Gabius
Publisher: John Wiley & Sons
ISBN: 3527614729
Category : Science
Languages : en
Pages : 663
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Book Description
A comprehensive survey of the topic, ranging from basic molecular research to clinical applications. Critical reviews by leading experts in each field summarize the state of knowledge and discuss the anticipated benefits of novel approaches and strategies. These include the impact of modern analysis techniques on glycobiology, the use of synthetic neoglycoproteins, or the clinical consequences of new insights into the physiological role of lectins and glycoconjugates in pathology, oncology, immunity, neuroscience and reproduction medicine. Throughout, the aim is to separate realistic applications from mere hopes.
Author: A.J. Rivett
Publisher: Elsevier Science
ISBN: 9780762303878
Category : Science
Languages : en
Pages : 0
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Book Description
This volume brings together a set of reviews that provide a summary of our current knowledge of the proteolytic machinery and of the pathways of protein breakdown of prokaryotic and eukaryotic cells. Intracellular protein degradation is much more than just a mechanism for the removal of incorrectly folded or damaged proteins. Since many short-lived proteins have important regulatory functions, proteolysis makes a significant contribution to many cellular processes including cell cycle regulation and transciptional control. In addition, limited proteolytic cleavage can provide a rapid and efficient mechanism of enzyme activation or inactivation in eukaryotic cells. In the first chapter, Maurizi provides an introduction to intracellular protein degradation, describes the structure and functions of bacterial ATP-dependent proteases, and explores the relationship between chaperone functions and protein degradation. Many of the principles also apply to eukaryotic cells, although the proteases involved are often not the same. Interestingly, homologues of one of the bacterial proteases, Ion protease, have been found in mitochondria in yeast and mammals, and homologues of proteasomes, which are found in all eukaryotic cells (see below), have been discovered in some eubacteria. Studies of proteolysis in yeast have contributed greatly to the elucidation of both lysosomal (vacuolar) and nonlysosomal proteolytic pathways in eukaryotic cells. Thumm and Wolf (chapter 2) describe studies that have elucidated the functions of proteasomes in nonlysosomal proteolysis and the contributions of lysosomal proteases to intracellular protein breakdown. Proteins can be selected for degradation by a variety of differen mechanisms. The ubiquitin system is one complex and highly regulated mechanism by which eukaryotic proteins are targetted for degradation by proteosomes. In chapter 3, Wilkinson reviews the components and functions of the ubiquitin system and considers some of the known substrates for this pathway which include cell cycle and transcriptional regulators. The structure and functions of proteosomes and their regulatory components are described in the two subsequent chapters by Tanaka and Tanahashi and by Dubiel and Rechsteiner. Proteasomes were the first known example of threonine proteases. They are multisubunit complexes that, in addition to being responsible for the turnover of most short-lived nuclear and cytoplasmic protein, are also involved in antigen processing for presentation by the MHC class I pathway. Recent studies reviewed by McCracken and colleagues (chapter 6) lead to the exciting conclusion that some ER-associated proteins are degraded by cytosolic proteasomes. Lysosomes are responsible for the degradation of long-lived proteins and for the enhanced protein degradation observed under starvation conditions. In chapter 7 Knecht and colleagues review the lysosomal proteases and describe studies of the roles of lysosomes and the mechanisms for protein uptake into lysosomes. Methods of measuring the relative contribution of different proteolytic systems (e.g., ubiquitin-proteasome pathway, calcium-dependent proteases, lysosomes) to muscle protein degradation, and the conclusions from such studies, are reviewed by Attai and Taillinder in the following chapter. Finally, proteases play an important role in signaling apoptosis by catalyzing the limited cleavage of enzymes. Mason and Beyette review the role of the major players, caspases, which are both activated by and catalyze limite proteolysis, and also consider the involvement of other protoelytic enzymes in this pathway leading cell death.
Author: H. Osada
Publisher: Springer Science & Business Media
ISBN: 4431659277
Category : Science
Languages : en
Pages : 261
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Book Description
Rapid advances in the study of the molecular basis of mammalian cell proliferation, differentiation, and apoptosis have made it possible to develop new screening systems for isolating from microbial metabolites specific inhibitors of mammalian cell functions. "Bioprobes" is the term used to describe these inhibitors, which are extremely useful agents in investigating the molecular and chemical regulation of eukaryotic cell function and apoptosis. Another area where bioprobes are playing an important role is research into immune cell function. This book is the first to present the groundbreaking applications of bioprobes as tools for biochemical research. A large appendix contains the chemical structure, origin, function, key references, and other essential data for more than 80 important bioprobes. The information for each bioprobe is shown in a two-page display, in an easy-to-use format for identifying specific bioprobes for investigation of cell function.
