Rab GTPase-activating Proteins at the Golgi:endosome Interface PDF Download
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Author: Ryan Michael Nottingham
Publisher: Stanford University
ISBN:
Category :
Languages : en
Pages : 166
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Book Description
Rab GTPases are master regulators of membrane trafficking in eukaryotic cells. With GTP bound, they regulate trafficking by recruiting effectors to specific membrane-bound compartments. GTPase-activating proteins (GAPs) stimulate a Rab's intrinsic rate of GTP hydrolysis, thus inactivating the Rab by converting bound GTP to GDP. Regulation of Rab proteins links the formation and breakdown of sequential, Rab-regulated membrane domains in the secretory and endocytic pathways. This thesis presents the characterization of a novel RabGAP, RUTBC1. RUTBC1 binds Rab9 in vitro and in cells through interactions with its N-terminus. Overexpression of RUTBC1 only slightly disrupts MPR trafficking and RUTBC1 does not function as a GAP for Rab9. In vitro biochemical screening of Rab proteins revealed that RUTBC1 has GAP activity toward Rab33b and Rab32. These data suggest that RUTBC1 might function to link inactivation of these Rabs in relation to a Rab9 microdomain, in support of the existence of a Rab cascade at the interface between the Golgi apparatus and endosomes. Depletion of RUTBC1 unexpectedly led to concomitant depletion of Atg16L1. Atg16L1 has an established and essential role in macroautophagy, a highly conserved cellular recycling process. Overexpression of Atg16L1 caused the formation of large puncta in the cytoplasm, which are also labeled by endogenous RUTBC1 and may represent autophagosomes. Atg16L1 is a known Rab33b effector, suggesting that Rab33b, RUTBC1 and Atg16L1 function together to regulate autophagosome formation. Finally, RUTBC2, which is highly related to RUTBC1, also binds specifically to Rab9. In vitro biochemical screening for RUTBC2's Rab substrates showed that RUTBC2 had highest GAP activity toward Rab34 and Rab36, two very similar Rabs thought to play a role in secretion. The difference in substrate specificity between RUTBC1 and RUTBC2 further exemplifies the highly complex integration of diverse membrane trafficking pathways in mammalian cells.
Author: Ryan Michael Nottingham
Publisher: Stanford University
ISBN:
Category :
Languages : en
Pages : 166
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Book Description
Rab GTPases are master regulators of membrane trafficking in eukaryotic cells. With GTP bound, they regulate trafficking by recruiting effectors to specific membrane-bound compartments. GTPase-activating proteins (GAPs) stimulate a Rab's intrinsic rate of GTP hydrolysis, thus inactivating the Rab by converting bound GTP to GDP. Regulation of Rab proteins links the formation and breakdown of sequential, Rab-regulated membrane domains in the secretory and endocytic pathways. This thesis presents the characterization of a novel RabGAP, RUTBC1. RUTBC1 binds Rab9 in vitro and in cells through interactions with its N-terminus. Overexpression of RUTBC1 only slightly disrupts MPR trafficking and RUTBC1 does not function as a GAP for Rab9. In vitro biochemical screening of Rab proteins revealed that RUTBC1 has GAP activity toward Rab33b and Rab32. These data suggest that RUTBC1 might function to link inactivation of these Rabs in relation to a Rab9 microdomain, in support of the existence of a Rab cascade at the interface between the Golgi apparatus and endosomes. Depletion of RUTBC1 unexpectedly led to concomitant depletion of Atg16L1. Atg16L1 has an established and essential role in macroautophagy, a highly conserved cellular recycling process. Overexpression of Atg16L1 caused the formation of large puncta in the cytoplasm, which are also labeled by endogenous RUTBC1 and may represent autophagosomes. Atg16L1 is a known Rab33b effector, suggesting that Rab33b, RUTBC1 and Atg16L1 function together to regulate autophagosome formation. Finally, RUTBC2, which is highly related to RUTBC1, also binds specifically to Rab9. In vitro biochemical screening for RUTBC2's Rab substrates showed that RUTBC2 had highest GAP activity toward Rab34 and Rab36, two very similar Rabs thought to play a role in secretion. The difference in substrate specificity between RUTBC1 and RUTBC2 further exemplifies the highly complex integration of diverse membrane trafficking pathways in mammalian cells.
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: M. A. Hayat
Publisher: Academic Press
ISBN: 0128094273
Category : Medical
Languages : en
Pages : 431
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Book Description
Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Author: Engelbert Buxbaum
Publisher: Springer
ISBN: 331919920X
Category : Science
Languages : en
Pages : 521
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Book Description
This book serves as an introduction to protein structure and function. Starting with their makeup from simple building blocks, called amino acids, the 3-dimensional structure of proteins is explained. This leads to a discussion how misfolding of proteins causes diseases like cancer, various encephalopathies, or diabetes. Enzymology and modern concepts of enzyme kinetics are then introduced, taking into account the physiological, pharmacological and medical significance of this often neglected topic. This is followed by thorough coverage of hæmoglobin and myoglobin, immunoproteins, motor proteins and movement, cell-cell interactions, molecular chaperones and chaperonins, transport of proteins to various cell compartments and solute transport across biological membranes. Proteins in the laboratory are also covered, including a detailed description of the purification and determination of proteins, as well as their characterisation for size and shape, structure and molecular interactions. The book emphasises the link between protein structure, physiological function and medical significance. This book can be used for graduate and advanced undergraduate classes covering protein structure and function and as an introductory text for researchers in protein biochemistry, molecular and cell biology, chemistry, biophysics, biomedicine and related courses. About the author: Dr. Buxbaum is a biochemist with interest in enzymology and protein science. He has been working on the biochemistry of membrane transport proteins for nearly thirty years and has taught courses in biochemistry and biomedicine at several universities.
Author: Nava Segev
Publisher: Springer Science & Business Media
ISBN: 038793877X
Category : Science
Languages : en
Pages : 459
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Book Description
This book covers the past, present and future of the intra-cellular trafficking field, which has made a quantum leap in the last few decades. It details how the field has developed and evolved as well as examines future directions.
Author: Gareth Griffiths
Publisher: Springer Science & Business Media
ISBN: 3642770959
Category : Science
Languages : en
Pages : 477
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Book Description
Electron microscopy in the biological sciences can be divided into two disciplines. The first, concerned with high resolution detail of particles or periodic structures, is mostly based on sound theoretical principles of physics. The second, by far the larger discipline, is interested in the information obtainable from thin sections. The theoretical back ground to those groups of techniques for preparing and looking at thin sections is often inexact and "loose", for want of a better word. What should be chemistry is often closer to alchemy. This kind of electron microscopy is often enshrined with mystical recipes, handed down from generation to generation. Admittedly, many of the processes involved, such as those required to embed tissue in epoxy resins, involve multiple interconnected steps, which make it difficult to follow the details of anyone of these steps. If all these steps are shrouded in some mystery, however, can one really trust the final image that emerges on the EM screen? When we present the data in some semi quantitative form is there really no better way to do it than to categorize the parameters with ++, +/-, etc? What happens when one labels the sections with antibodies? Does the whole business necess arily need to be more of an "art" than a "science"? Upon reflecting on these problems in 1981, I had the impression that many of the multi-authored textbooks that existed then (and that have appeared since) tended to exacerbate or at least perpetuate this
Author: Olivier Binda
Publisher: Academic Press
ISBN: 012802609X
Category : Science
Languages : en
Pages : 468
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Book Description
Chromatin Signaling and Diseases covers the molecular mechanisms that regulate gene expression, which govern everything from embryonic development, growth, and human pathologies associated with aging, such as cancer. This book helps researchers learn about or keep up with the quickly expanding field of chromatin signaling. After reading this book, clinicians will be more capable of explaining the mechanisms of gene expression regulation to their patients to reassure them about new drug developments that target chromatin signaling mechanisms. For example, several epigenetic drugs that act on chromatin signaling factors are in clinical trials or even approved for usage in cancer treatments, Alzheimer's, and Huntington's diseases. Other epigenetic drugs are in development to regulate various class of chromatin signaling factors. To keep up with this changing landscape, clinicians and doctors will need to stay familiar with genetic advances that translate to clinical practice, such as chromatin signaling. Although sequencing of the human genome was completed over a decade ago and its structure investigated for nearly half a century, molecular mechanisms that regulate gene expression remain largely misunderstood. An emerging concept called chromatin signaling proposes that small protein domains recognize chemical modifications on the genome scaffolding histone proteins, facilitating the nucleation of enzymatic complexes at specific loci that then open up or shut down the access to genetic information, thereby regulating gene expression. The addition and removal of chemical modifications on histones, as well as the proteins that specifically recognize these, is reviewed in Chromatin Signaling and Diseases. Finally, the impact of gene expression defects associated with malfunctioning chromatin signaling is also explored. - Explains molecular mechanisms that regulate gene expression, which governs everything from embryonic development, growth, and human pathologies associated with aging - Educates clinicians and researchers about chromatin signaling, a molecular mechanism that is changing our understanding of human pathology - Explores the addition and removal of chemical modifications on histones, the proteins that specifically recognize these, and the impact of gene expression defects associated with malfunctioning chromatin signaling - Helps researchers learn about the quickly expanding field of chromatin signaling
Author:
Publisher: Elsevier
ISBN: 0124171834
Category : Science
Languages : en
Pages : 499
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Book Description
This new volume of Methods in Cell Biology looks at methods for analyzing of golgi complex function. Chapters cover such topics as in vitro reconstitution systems, fluorescence-based analysis of trafficking in mammalian cells and high content screening. With cutting-edge material, this comprehensive collection is intended to guide researchers for years to come. - Covers sections on model systems and functional studies, imaging-based approaches and emerging studies - Chapters are written by experts in the field - Cutting-edge material
Author:
Publisher: Academic Press
ISBN: 0080585108
Category : Science
Languages : en
Pages : 477
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Book Description
Current Topics in Membranes
Author: Masaharu Takigawa
Publisher: World Scientific
ISBN: 1783260335
Category : Science
Languages : en
Pages : 324
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Book Description
The CCN Proteins are thought to play key roles in the biology of normal cell, tissue, organ, and body, and altered expression of CCN proteins is associated with several pathologies, including fibrosis and cancer. Because of its importance, the CCN field is expanding at a fast pace. Research articles in this field have recently increased logarithmically, and a book that is up-to-date, comprehensive, authoritative and affords insights into the biological roles of CCN proteins, is timely.CCN Protein: A New Family of Cell Growth and Differentiation Regulators presents the most recent progress in the field of CCN proteins, a new family of secretory signaling molecules that are involved in several fundamental biological progress. These proteins share a unique multimodular organization and present a partial identity with four families of regulatory proteins controling growth and development. The book covers the roles of CCN proteins in the control of cell proliferation and differentiation during normal development, wound repair, chondrogenesis and bone development, angiogenesis, tissue regeneration, fibrosis, renal diseases and cancer development.
