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The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms
by
Christoforidis, Savvas
, Lindsay, Margaret R
, Wilm, Matthias
, Uttenweiler-Joseph, Sandrine
, Parton, Robert G
, Schnatwinkel, Carsten
, Zerial, Marino
in
Adenoviridae - genetics
/ Androstadienes - pharmacology
/ Animals
/ Biochemistry, Molecular Biology
/ Cell Biology
/ Cell Line
/ Cell Line, Tumor
/ Cell Membrane - metabolism
/ Cloning, Molecular
/ Colleges & universities
/ Dogs
/ Down-Regulation
/ Endocytosis - physiology
/ Endosomes - metabolism
/ Enzyme Inhibitors - pharmacology
/ Epidermal growth factor
/ Epithelial Cells - cytology
/ Fibroblasts - metabolism
/ Gene Expression Regulation
/ GTP Phosphohydrolases - chemistry
/ Humans
/ Inositol Phosphates - chemistry
/ Intracellular Signaling Peptides and Proteins - genetics
/ Intracellular Signaling Peptides and Proteins - physiology
/ Kidneys
/ Life Sciences
/ Liposomes - metabolism
/ Mammals
/ Mice
/ Microscopy, Confocal
/ Microscopy, Video
/ Motility
/ Movement
/ NIH 3T3 Cells
/ Pinocytosis
/ Plasmids - metabolism
/ Protein Binding
/ Protein Structure, Tertiary
/ Proteins
/ rab5 GTP-Binding Proteins - physiology
/ Recombinant Proteins - chemistry
/ RNA Interference
/ Time Factors
2004
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The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms
by
Christoforidis, Savvas
, Lindsay, Margaret R
, Wilm, Matthias
, Uttenweiler-Joseph, Sandrine
, Parton, Robert G
, Schnatwinkel, Carsten
, Zerial, Marino
in
Adenoviridae - genetics
/ Androstadienes - pharmacology
/ Animals
/ Biochemistry, Molecular Biology
/ Cell Biology
/ Cell Line
/ Cell Line, Tumor
/ Cell Membrane - metabolism
/ Cloning, Molecular
/ Colleges & universities
/ Dogs
/ Down-Regulation
/ Endocytosis - physiology
/ Endosomes - metabolism
/ Enzyme Inhibitors - pharmacology
/ Epidermal growth factor
/ Epithelial Cells - cytology
/ Fibroblasts - metabolism
/ Gene Expression Regulation
/ GTP Phosphohydrolases - chemistry
/ Humans
/ Inositol Phosphates - chemistry
/ Intracellular Signaling Peptides and Proteins - genetics
/ Intracellular Signaling Peptides and Proteins - physiology
/ Kidneys
/ Life Sciences
/ Liposomes - metabolism
/ Mammals
/ Mice
/ Microscopy, Confocal
/ Microscopy, Video
/ Motility
/ Movement
/ NIH 3T3 Cells
/ Pinocytosis
/ Plasmids - metabolism
/ Protein Binding
/ Protein Structure, Tertiary
/ Proteins
/ rab5 GTP-Binding Proteins - physiology
/ Recombinant Proteins - chemistry
/ RNA Interference
/ Time Factors
2004
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The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms
by
Christoforidis, Savvas
, Lindsay, Margaret R
, Wilm, Matthias
, Uttenweiler-Joseph, Sandrine
, Parton, Robert G
, Schnatwinkel, Carsten
, Zerial, Marino
in
Adenoviridae - genetics
/ Androstadienes - pharmacology
/ Animals
/ Biochemistry, Molecular Biology
/ Cell Biology
/ Cell Line
/ Cell Line, Tumor
/ Cell Membrane - metabolism
/ Cloning, Molecular
/ Colleges & universities
/ Dogs
/ Down-Regulation
/ Endocytosis - physiology
/ Endosomes - metabolism
/ Enzyme Inhibitors - pharmacology
/ Epidermal growth factor
/ Epithelial Cells - cytology
/ Fibroblasts - metabolism
/ Gene Expression Regulation
/ GTP Phosphohydrolases - chemistry
/ Humans
/ Inositol Phosphates - chemistry
/ Intracellular Signaling Peptides and Proteins - genetics
/ Intracellular Signaling Peptides and Proteins - physiology
/ Kidneys
/ Life Sciences
/ Liposomes - metabolism
/ Mammals
/ Mice
/ Microscopy, Confocal
/ Microscopy, Video
/ Motility
/ Movement
/ NIH 3T3 Cells
/ Pinocytosis
/ Plasmids - metabolism
/ Protein Binding
/ Protein Structure, Tertiary
/ Proteins
/ rab5 GTP-Binding Proteins - physiology
/ Recombinant Proteins - chemistry
/ RNA Interference
/ Time Factors
2004
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The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms
Journal Article
The Rab5 Effector Rabankyrin-5 Regulates and Coordinates Different Endocytic Mechanisms
2004
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Overview
The small GTPase Rab5 is a key regulator of clathrin-mediated endocytosis. On early endosomes, within a spatially restricted domain enriched in phosphatydilinositol-3-phosphate [PI(3)P], Rab5 coordinates a complex network of effectors that functionally cooperate in membrane tethering, fusion, and organelle motility. Here we discovered a novel PI(3)P-binding Rab5 effector, Rabankyrin-5, which localises to early endosomes and stimulates their fusion activity. In addition to early endosomes, however, Rabankyrin-5 localises to large vacuolar structures that correspond to macropinosomes in epithelial cells and fibroblasts. Overexpression of Rabankyrin-5 increases the number of macropinosomes and stimulates fluid-phase uptake, whereas its downregulation inhibits these processes. In polarised epithelial cells, this function is primarily restricted to the apical membrane. Rabankyrin-5 localises to large pinocytic structures underneath the apical surface of kidney proximal tubule cells, and its overexpression in polarised Madin-Darby canine kidney cells stimulates apical but not basolateral, non-clathrin-mediated pinocytosis. In demonstrating a regulatory role in endosome fusion and (macro)pinocytosis, our studies suggest that Rab5 regulates and coordinates different endocytic mechanisms through its effector Rabankyrin-5. Furthermore, its active role in apical pinocytosis in epithelial cells suggests an important function of Rabankyrin-5 in the physiology of polarised cells.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Androstadienes - pharmacology
/ Animals
/ Biochemistry, Molecular Biology
/ Dogs
/ Enzyme Inhibitors - pharmacology
/ GTP Phosphohydrolases - chemistry
/ Humans
/ Inositol Phosphates - chemistry
/ Intracellular Signaling Peptides and Proteins - genetics
/ Intracellular Signaling Peptides and Proteins - physiology
/ Kidneys
/ Mammals
/ Mice
/ Motility
/ Movement
/ Proteins
/ rab5 GTP-Binding Proteins - physiology
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