Sorting And Recycling Endosomes
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Sorting And Recycling Endosomes
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Author :
language : en
Publisher: Academic Press
Release Date : 2015-09-14
Sorting And Recycling Endosomes written by and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-09-14 with Science categories.
Sorting and Recycling Endosomes provides the latest information on endosomes, the receiving compartment for endocytosed cargos, and the donor compartment and sorting station for cargos designated to lysosomes, Golgi, or plasma membrane. In recent years, the importance of endosomes as a sorting and recycling compartment has become increasingly appreciated. As such, scientists from various fields of cell biology, membrane traffic, and beyond, see the needs to communicate and learn about the methods used to investigate the dynamics and functions of endosomes. This book brings together specialists from the field who contribute their expertise on a broad range of biomedical topics that will provide ideal reading for researchers interested in endosomal sorting and recycling. This volume covers the approaches necessary to study the key components that mediate the generation and transport of membrane-bounded carriers from the endosomes, and how membrane trafficking machinery is coordinated with cytoskeletons during these processes. In addition to studies carried out in mammalian cells, other model systems such as worm and yeast are also included. Provides the latest information on endosomes, the receiving compartment for endocytosed cargos, and the donor compartment and sorting station for cargos designated to lysosomes, Golgi, or plasma membrane. Covers an increasingly appreciated field in cell biology Includes both established and new technologies Brings together specialists from the field who contribute their expertise on a broad range of biomedical topics that will provide ideal reading for researchers interested in endosomal sorting and recycling
Endocytic Recycling And Regulation Of The Early To Recycling Endosome Transition
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Author : Ou Liu
language : en
Publisher:
Release Date : 2015
Endocytic Recycling And Regulation Of The Early To Recycling Endosome Transition written by Ou Liu and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015 with Biological transport categories.
Endocytic recycling is the process by which cells return internalized cargos and receptors back to plasma membrane. Efficient recycling of cargos requires ordered transport of cargos from early endosome to recycling endosome. This is mainly achieved through the coordination of small GTPase RAB-5 and RAB-10. The small GTPase RAB-5 is a master regulator of cargo sorting at the early endosome and RAB-10 is a key resident of the recycling endosome. Countercurrent cascades of GEFs and GAPs for Rab proteins have been proposed to mediate Rab conversion, a process in which early acting Rabs are inactivated by later acting Rabs. Here we demonstrate that a downstream Rab protein, RAB-10, binds to and recruits a RAB-5 GAP, TBC-2, onto endosomes to inactivate the upstream Rab, RAB-5. This process is critical for proper relay of cargos from RAB-5 controlled early endosomes to RAB-10 regulated recycling endosomes. Lack of TBC-2 disrupted RAB-5/RAB-10 interaction and caused accumulation of recycling cargo hTAC-GFP in a malfunctioned hybrid early-recycling endosome compartment. Furthermore, our study showed that this cargo transition process from early to recycling endosome also requires the concerted effort by a BAR-domain protein AMPH-1, which acts as a binding partner and a contributor to the recruitment of TBC-2 on endosomes. In addition, the C. elegans Rac1 homolog CED-10 can also bind and recruit it to endosomes. Taken together, our worked showed that RAB-10, AMPH-1 and CED-10 act in a concerted manner and recruits TBC-2 to inactivate RAB-5. These interactions are essential for early-to-recycling endosome transition and endocytic recycling. We further demonstrated here that RAB-10, recruits CNT-1, the C. elegans homolog of mammalian ACAP1 and ACAP2 (Arf6 GTPase-activating proteins) to inactivate ARF-6 and downregulate endosomal PI(4,5)P2, a key phosphoinositide in membrane traffic.
Endosomes
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Author : Ivan Dikic
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-05-07
Endosomes written by Ivan Dikic and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-05-07 with Science categories.
Endosomes are a heterogeneous population of endocytic vesicles and tubules that have captivated the interest of biologists for many years, partly due to their important cellular functions and partly due to their intriguing nature and dynamics. Endosomes represent a fascinating interconnected network of thousands of vesicles that transport various cargoes, mainly proteins and lipids, to distant cellular destinations. How endosomes function, what co-ordinates the molecular determinants at each step of their dynamic life cycle and what their biological and medical relevance is, are among the questions addressed in this book.
Membrane Sorting In The Endocytic Pathway
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Author : Valentina Mercanti
language : en
Publisher:
Release Date : 2007
Membrane Sorting In The Endocytic Pathway written by Valentina Mercanti and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007 with categories.
During my thesis work I studied membrane sorting in the endocytic pathway, in mammalian cells and in the amoeba "Dictyostelium discoideum". In the first part (1), I studied sorting of membrane proteins devoid of known endocytosis signals. My results show that, in addition to cytoplasmic tails of membrane proteins, then transmembrane regions determine whether they are excluded or not from clathrincoated pits, and thus controls their access to endosomal compartmemts. In the second part (2), I studied membrane sorting during phagocytosis and macropinocytosis. I used for this the amoeba "Dictyostelium discoideum". My results show that several plasma membrane proteins are excluded from the membrane of the newly formed phagosome. This exclusion starts in the membrane delimiting the phagocytic and the macropinocytic cups. Analysis of mutant strains revealed that clathrin-associated adaptor complexes were not necessary for this selective exclusion. In third part (3), I characterized the previously uncharacterized recycling endosomes in "Dictyostelium discoideum"
Characterization Of Endocytic Recycling And Sorting Of Glycosylphosphatidylinositol Anchored Proteins In Fibroblastic Cell Lines
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Author : Mohammad Refaei
language : en
Publisher:
Release Date : 2010
Characterization Of Endocytic Recycling And Sorting Of Glycosylphosphatidylinositol Anchored Proteins In Fibroblastic Cell Lines written by Mohammad Refaei 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.
Regulation Of Endocytic Recycling In Caenorhabditis Elegans
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Author : Anbing Shi
language : en
Publisher:
Release Date : 2010
Regulation Of Endocytic Recycling In Caenorhabditis Elegans written by Anbing Shi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Caenorhabditis elegans categories.
Eukaryotic endocytic pathway is important for the uptake, sorting, and the subsequential recycling or degradation processes of various cargos. It has been shown that the RME-1/EHD1 is a critical regulator of endocytic recycling. In C. elegans and MDCK cells, small GTPase RAB-10 has been specifically implicated in clathrin-independent cargo recycling. Alternatively, some cargos will be recycled from sorting endosomes to Golgi, and retromer complex was shown to be crucial for this transport in yeast and mammalian cells. In our studies, we analyzed RME-1 and RAB-10 regulated recycling pathway, exploring additional players in the process. First, we demonstrated that ALX-1 is required for endocytic recycling of specific basolateral cargo. The interaction of ALX-1 with RME-1 is required for this recycling process. In our yeast two-hybrid screen for RAB-10-interacting proteins, EHBP-1 and Arf6 GAP/CNT-1 were recovered and revealed to function together with RAB-10 regulating clathrin-independent cargo recycling. Loss of either EHBP-1 or CNT-1 produced rab-10-like cargo transport defects. Furthermore, we showed that EHBP-1 functions, as an unconventional effector, upstream of RAB-10. Nevertheless, similar to canonical Rab effectors, CNT-1 requires RAB-10 for the proper endosome localization. Collectively, our results demonstrate the functional connections of ALX-1/RME-1 and RAB-10/EHBP-1/CNT-1, provided insights into the detail mechanisms of RME-1 and RAB-10 recycling regulation. We also studied the retromer regulated retrograde transport in C. elegans. We demonstrated the physical interaction of RME-8 with retromer component ALX-1. Additionally, we showed that loss-of-function in rme-8 or snx-1, or depletion of C. elegans Hsc70 (HSP-1) by RNAi, disrupts endosome to Golgi transport of the retromer-dependent cargo protein MIG-14. Furthermore, we identified a previously unsuspected mechanism for the regulation of endosomal clathrin that is required for retrograde transport. We showed that loss of either RME-8, SNX-1 or HSP-1 leads to endosomal clathrin dynamics defect. Our work indicates that, through RME-8 and Hsc70, the retromer acts to limit clathrin accumulation, a prerequisite for the recycling of retrograde cargo.
Signal Dependent Membrane Protein Sorting In The Endocytic Pathway
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Author : Charles Gregory Odorizzi
language : en
Publisher:
Release Date : 1996
Signal Dependent Membrane Protein Sorting In The Endocytic Pathway written by Charles Gregory Odorizzi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1996 with categories.
Modulation Of Cargo Transport And Sorting Through Endosome Motility And Positioning
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Author :
language : en
Publisher:
Release Date : 2005
Modulation Of Cargo Transport And Sorting Through Endosome Motility And Positioning written by 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.
Utilizing various systems such as cell-based assays but also multicellular organisms such as Drosophila melanogaster and C.elegans, for example, the endocytic system has been shown to consist of a network of biochemically and morphologically distinct organelles that carry out specialized tasks in the uptake, recycling and catabolism of growth factors and nutrients, serving a plethora of key biological functions (Mellman, 1996). Different classes of endosomes were found to exhibit a characteristic intracellular steady state distribution. This distribution pattern observed at steady state results from a dynamic interaction of endosomes with the actin and the microtubule cytoskeleton. It remains unclear, however, which microtubule-based motors besides Dynein control the intracellular distribution and motility of early endosomes and how their function is integrated with the sorting and transport of cargo. The first part of this thesis research outlines the search for such motor. I describe the identification of KIF16B which functions as a novel endocytic motor protein. This molecular motor, a kinesin-3, transports early endosomes to the plus end of microtubules, in a process regulated by the small GTPase Rab5 and its effector, the phosphatidylinositol-3-OH kinase hVPS34. In vivo, KIF16B overexpression relocated early endosomes to the cell periphery and inhibited transport to the degradative pathway. Conversely, expression of dominant-negative mutants or ablation of KIF16B by RNAi caused the clustering of early endosomes to the peri-nuclear region, delayed receptor recycling to the plasma membrane and accelerated degradation. These results suggest that KIF16B, by regulating the plus end motility of early endosomes, modulates the intracellular localization of early endosomes and the balance between receptor recycling and degradation. In displaying Rab5 and PI(3)P-containing cargo selectivity, a remarkable property of KIF16B is that it is subjected to the same regulatory p.
Endocytic Recycling In Caenorhabditis Elegans
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Author : Adenrele Madeline Gleason
language : en
Publisher:
Release Date : 2016
Endocytic Recycling In Caenorhabditis Elegans written by Adenrele Madeline Gleason and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016 with Caenorhabditis elegans categories.
The power of conservation is exemplified in the C. elegans intestinal epithelia. As a model to study endocytic recycling, molecular transport regulators have been characterized in this genetically tractable system. In this dissertation, I describe the molecular requirements for Syndpin/SDPN-1 in vivo. Proteoliposome assays confirm that full-length SDPN-1 is capable of tubulating acidic liposomes in vitro. As a likely accessory protein, SDPN-1 coordinates the exit of recycling cargo from the early endosome. I propose that Syndapin/SDPN-1 facilitates this transport step through the localized recruitment of actin to early endosomes. In addition, the worm intestine provides a lucid understanding of the endosomal determinates that coordinate TGFÎ2 signaling. We report TGFÎ2 signaling and internalization require Clathrin-Dependent Endocytosis (CDE). Furthermore, post internalization of the receptors result in the sorting of the type I and the type II receptors into distinct molecular sorting complexes. Mutants defective in retromer-dependent recycling missort their type I SMA-6 to the lysosome and impair signaling. Alternatively, the type II receptor, DAF-4 (dauer formation defective-4) is returned through the ARF-6 (ADP-ribosylation factor-6) dependent recycling pathway.
Characterizing The Role Of Endocytic Recycling In The Maintenance Of Polarity In The Caenorhabditis Elegans Embryo
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Author :
language : en
Publisher:
Release Date : 2012
Characterizing The Role Of Endocytic Recycling In The Maintenance Of Polarity In The Caenorhabditis Elegans Embryo written by and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012 with categories.
In biology, the asymmetric localization of molecules or organelles within a single cell is crucial for the specification of cell types found in multicellular organisms. The mechanisms that polarize a cell are widely conserved. The PAR polarity complex and the small GTPase Cdc42 are regulate cellular polarity in embryos, neuronal cells and epithelial cells. A balance between endocytosis, recycling and lateral diffusion has been described as a key mechanism that stabilizes polarized protein localization. However, it remains poorly understood how exactly endocytosis and recycling could achieve this function in higher eukaryotic cells. In this dissertation, I have characterized an endocytic mechanism that participates in the maintenance of PAR asymmetry in the C. elegans embryo. C. elegans dynamin, DYN-1, localizes to cortical puncta that become enriched at the anterior half of the embryo, where endocytosis occurs primarily during maintenance phase. Depletion of DYN-1 significantly reduces the enrichment of endocytosis, and destabilization PAR and CDC-42 asymmetry during polarity maintenance phase is observed. I found that the anterior polarity cue, PAR-6, localizes to cytoplasmic puncta that emerge from the cortex into the cell from dynamin-rich sites. Taken together, this work suggests that dynamin-dependent endocytosis of polarity cues plays a role in stabilizing polarity during maintenance phase. In the subsequent study, I found that the Arp2/3 complex achieves both of these roles. Depletion of the ARX-2 specifically disrupts maintenance of actin and DYN-1 foci. Localizations of polarity cues are destabilized in a manner similar to that observed in dyn-1 RNAi-treated embryos. I do not observe disruptions in endocytosis, but do observe significantly larger early endosomes and accumulations of cytoplasmic PAR-6 in association with these endosomes. I suggest that I have uncovered an actin-dependent mechanism for the rapid recycling of internalized anterior polarity cues, and this contributes to the stable localization at the cortex. Together, my work has characterized a novel mechanism in which dynamin participates in the internalization of polarity cues, and Arp2/3-mediated actin dynamics appears to participate in the regulation of their sorting and recycling at the early endosome. Efficient function of these events contributes to the stabilization of cortical asymmetry.