Rab Gtpases And Membrane Trafficking
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Rab Gtpases And Membrane Trafficking
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Author : Guangpu Li
language : en
Publisher: Bentham Science Publishers
Release Date : 2012-05-21
Rab Gtpases And Membrane Trafficking written by Guangpu Li and has been published by Bentham Science Publishers this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-05-21 with Science categories.
"Ypt/Rab GTPases form the largest branch of the Ras-related small GTPase superfamily and regulate intracellular membrane trafficking in all eukaryotes. Since their discovery over two decades ago, a wealth of information has accumulated about the roles that"
Rab Gtpase Activating Proteins At The Golgi Endosome Interface
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Author : Ryan Michael Nottingham
language : en
Publisher: Stanford University
Release Date : 2010
Rab Gtpase Activating Proteins At The Golgi Endosome Interface written by Ryan Michael Nottingham and has been published by Stanford University this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
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.
Insights Into Cellular Complexity And The Evolution Of Membrane Trafficking From A Survey Of Rab Gtpases In Tetrahymena Thermophila
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Author : Lydia Jane Bright
language : en
Publisher:
Release Date : 2011
Insights Into Cellular Complexity And The Evolution Of Membrane Trafficking From A Survey Of Rab Gtpases In Tetrahymena Thermophila written by Lydia Jane Bright and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011 with categories.
I have also defined a subset of the Rab family as Rab-like proteins (RABLs), 25 in total, that are missing the prenylation motif that determines each Rab's attachment to membranes.
Rab Gtpases
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Author : Guangpu Li (Molecular biologist)
language : en
Publisher:
Release Date : 2021
Rab Gtpases written by Guangpu Li (Molecular biologist) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with Guanosine triphosphatase categories.
This second edition volume expands on the previous edition with a discussion of new research and discoveries in the Rab field. Chapters in this book cover topics such as new information on Rab regulation and localization; interaction; function; and diseases. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Rab GTPases: Methods and Protocols, Second Edition is a valuable resource for scientists working in the fields of Rab and other small GTPases, and beyond.
Rab Gtpase Activating Proteins At The Golgi Endosome Interface
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Author : Ryan Michael Nottingham
language : en
Publisher:
Release Date : 2010
Rab Gtpase Activating Proteins At The Golgi Endosome Interface written by Ryan Michael Nottingham and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
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.
Rab Gtpases
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Author : Guangpu Li (Molecular biologist)
language : en
Publisher:
Release Date : 2015
Rab Gtpases written by Guangpu Li (Molecular biologist) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with Biochemistry categories.
This volume covers the latest technological advances in the characterization of the biosynthesis and functions of Rab GTPases and their regulation by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). The book consists of 28 chapters, and starts with an overview of the Rab GTPase family. The next few chapters describe systematic approaches to the identification and classification of Rabs and Rab GAPs, as well as the detection of Rab isoprenylation and membrane distribution. The last few chapters examine the biochemical and functional properties of individual Rabs in the order of exocytic, recycling, and endocytic Rabs. Written in the highly successful Methods of Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Instructive and practical, Rab GTPases: Methods and Protocols approaches each topic with great detail and is a valuable resource for researchers and students interested in the field of Rab GTPases.
Gtpases Regulating Membrane Targeting And Fusion
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Author : W. E. Balch
language : en
Publisher: Gulf Professional Publishing
Release Date : 2005-12-13
Gtpases Regulating Membrane Targeting And Fusion written by W. E. Balch and has been published by Gulf Professional Publishing this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005-12-13 with Science categories.
Rab GTPases now comprise a family of >63 members. They are emerging as the key hub element controlling the membrane architecture of eukaryotic cells. They are intimately involved in vesicle targeting and fusion in both the endocytic and exocytic pathways and direct the assembly and disassembly of protein complexes that include regulators (GEFs and GAPs), effectors (tethers/motors) and fusion components (SNAREs) that control membrane targeting and fusion. During the last 3 years the field has virtually exploded with the identification and characterization of many new Rab proteins and their effectors. Our understanding of how Rab GTPases control membrane function remains at its infancy. This volume of Methods in Enzymology, GTPases Regulating Membrane Targeting and Fusion, provides a wealth of new concepts, approaches and tools to study Rab proteins in the test tube and in living cells that will be of strong benefit to both established laboratories and new investigators in the field to elucidate Rab GTPase function in cellular development, differentiation and proliferation. Comprehensive overview of Rab GTPase phylogeny and systems biology Identification and characterization of Rab GEFs, GAPs and effectors General methodologies to study Rab GTPase function in vitro and in vivo using biochemical, molecular and microscopy approaches
The Rab Gtpases Ypt31 And Ypt32p Regulate Multiple Steps Of Membrane Traffic
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Author : Darinel Ortiz
language : en
Publisher:
Release Date : 2005
The Rab Gtpases Ypt31 And Ypt32p Regulate Multiple Steps Of Membrane Traffic written by Darinel Ortiz and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2005 with categories.
Membrane Binding Properties Of Rab Gtpases
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Author : Guillaume Kulakowski
language : en
Publisher:
Release Date : 2017
Membrane Binding Properties Of Rab Gtpases written by Guillaume Kulakowski and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017 with categories.
RAB GTPases are major regulators of vesicular trafficking and localize to specific compartments. Deciphering the molecular mechanisms governing RAB localization is thus critical to understand intracellular transport processes. We have managed, for the first time, to incorporate purified and prenylated RABs into artificial membranes. By doing so, we observed that RAB6, but not RAB1 or RAB5, is able to promote by itself vesicle tethering. We believe that RAB6 is able to interact in trans with itself and to consequently drive homotypic membrane tethering. In the main part of this study, we investigated the physicochemical membrane requirements necessary for RAB recruitment. RAB1, RAB5 and RAB6 were all found to only localize to disordered membrane domains and to preferentially bind to curved membranes. We demonstrated that this specific recruitment of RAB1, RAB5 and RAB6 is primarily dependent on the hydrophobic insertion of their prenyl group into lipid packing defects. In contrast, RAB35 recruitment was primarily dependent on the presence of negatively charged lipids and was found to be modulated, to a lesser extent, by lipid packing defects. Although RAB4 and RAB11 were effectively recruited to purified Golgi fractions, in an effector-independent manner, membrane charges and lipid packing defects were not sufficient to promote their recruitment to synthetic vesicles; suggesting that RAB4 and RAB11 require more demanding membrane physicochemical properties. Our work demonstrates that the properties of membranes are critical for the regulation of RAB specific membrane targeting.
The Regulation Of Rab13 In Endosomal Trafficking
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Author : Maria Ioannou
language : en
Publisher:
Release Date : 2016
The Regulation Of Rab13 In Endosomal Trafficking written by Maria Ioannou and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with categories.
"Rab GTPases are critical regulators of membrane trafficking and not surprisingly defects in Rabs contribute to various human diseases. For example, Rab13 is associated with several phenotypes associated with cancer, but the regulation of Rab13 in membrane trafficking is poorly understood. The general objective of this doctoral research was to study the function and regulation of Rab13 in endosomal trafficking. Rabs cycle between an active GTP-bound form and an inactive GDP-bound form. Upon activation by guanine nucleotide exchange factors, Rabs associate with membranes where they recruit effector molecules to mediate their downstream response. However, the spatio-temporal activation of Rab13 was unknown. Furthermore, the DENN-domain is an evolutionarily conserved protein module that functions enzymatically as guanine nucleotide exchange factors for Rabs. Here, we identified the DENN containing protein DENND2B as guanine nucleotide exchange factor for Rab13 and uncover a mechanism whereby activation of Rab13 by DENND2B in a complex with the Rab13 effector MICAL-L2 at the cell periphery drives cancer cell migration, invasion, and tumor metastasis. Furthermore, active Rabs typically anchor to membranes using a hydrophobic prenyl modification and dissociate from membranes upon inactivation. Here we discovered that Rab13 traffics on vesicles in its inactive form as part of a protein complex independent of prenylation. Therefore, in this doctoral thesis we have provided a detailed characterization of the regulation of Rab13 in endosomal trafficking. " --