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  • 1
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1999-08-24
    Description: Clathrin-mediated endocytosis is initiated by the recruitment of the clathrin adaptor protein AP-2 to the plasma membrane where the membrane protein synaptotagmin is thought to act as a docking site. AP-2 also interacts with endocytic motifs present in other cargo proteins. Peptides with a tyrosine-based endocytic motif stimulated binding of AP-2 to synaptotagmin and enhanced AP-2 recruitment to the plasma membrane of neuronal and non-neuronal cells. This suggests a mechanism by which nucleation of clathrin-coated pits is stimulated by the loading of cargo proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haucke, V -- De Camilli, P -- CA46128/CA/NCI NIH HHS/ -- NS36252/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1999 Aug 20;285(5431):1268-71.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Biology and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10455054" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex alpha Subunits ; Adaptor Proteins, Vesicular Transport ; Animals ; Binding Sites ; CHO Cells ; *Calcium-Binding Proteins ; Cattle ; Cell Membrane/metabolism ; Clathrin/*metabolism ; Coated Pits, Cell-Membrane/*metabolism ; Cricetinae ; *Endocytosis ; Membrane Glycoproteins/chemistry/*metabolism ; Membrane Proteins/*metabolism ; Nerve Tissue Proteins/chemistry/*metabolism ; Neurons/metabolism ; Oligopeptides/chemistry/metabolism/*pharmacology ; Phospholipase D/metabolism ; Protein Binding ; Rats ; Recombinant Fusion Proteins/metabolism ; Synaptic Membranes/*metabolism ; Synaptotagmins ; Tyrosine/chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2014-05-31
    Description: Synaptic vesicle recycling has long served as a model for the general mechanisms of cellular trafficking. We used an integrative approach, combining quantitative immunoblotting and mass spectrometry to determine protein numbers; electron microscopy to measure organelle numbers, sizes, and positions; and super-resolution fluorescence microscopy to localize the proteins. Using these data, we generated a three-dimensional model of an "average" synapse, displaying 300,000 proteins in atomic detail. The copy numbers of proteins involved in the same step of synaptic vesicle recycling correlated closely. In contrast, copy numbers varied over more than three orders of magnitude between steps, from about 150 copies for the endosomal fusion proteins to more than 20,000 for the exocytotic ones.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wilhelm, Benjamin G -- Mandad, Sunit -- Truckenbrodt, Sven -- Krohnert, Katharina -- Schafer, Christina -- Rammner, Burkhard -- Koo, Seong Joo -- Classen, Gala A -- Krauss, Michael -- Haucke, Volker -- Urlaub, Henning -- Rizzoli, Silvio O -- New York, N.Y. -- Science. 2014 May 30;344(6187):1023-8. doi: 10.1126/science.1252884.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Neurosciences, 37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. International Max Planck Research School Molecular Biology, 37077 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. ; Leibniz Institut fur Molekulare Pharmakologie, Department of Molecular Pharmacology and Cell Biology, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Bioanalytical Mass Spectrometry Group, Max-Planck-Institute for Biophysical Chemistry, 37077 Gottingen, Germany. Bioanalytics, Department of Clinical Chemistry, University Medical Center Gottingen, 37075 Gottingen, Germany. ; Department of Neuro- and Sensory Physiology, University of Gottingen Medical Center, European Neuroscience Institute, Cluster of Excellence Nanoscale Microscopy and Molecular Physiology of the Brain, Gottingen, Germany. srizzol@gwdg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24876496" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*metabolism/ultrastructure ; Exocytosis ; Imaging, Three-Dimensional ; Immunoblotting/methods ; Mass Spectrometry/methods ; Microscopy, Electron/methods ; Models, Neurological ; Presynaptic Terminals/chemistry/*metabolism/ultrastructure ; Protein Transport ; Rats ; Rats, Wistar ; Synaptic Vesicles/chemistry/*metabolism ; Synaptosomes/chemistry/*metabolism/ultrastructure ; Vesicular Transport Proteins/analysis/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-09-20
    Description: Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Faelber, Katja -- Posor, York -- Gao, Song -- Held, Martin -- Roske, Yvette -- Schulze, Dennis -- Haucke, Volker -- Noe, Frank -- Daumke, Oliver -- England -- Nature. 2011 Sep 18;477(7366):556-60. doi: 10.1038/nature10369.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Crystallography, Max-Delbruck-Centrum for Molecular Medicine, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. katja.faelber@mdc-berlin.de〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21927000" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Dynamin I/*chemistry/metabolism ; Dynamin II/genetics/metabolism ; GTP Phosphohydrolases/chemistry/metabolism ; Guanosine Triphosphate/metabolism ; HeLa Cells ; Humans ; Hydrolysis ; Models, Molecular ; Molecular Dynamics Simulation ; *Nucleotides ; Protein Binding ; Protein Structure, Tertiary ; Signal Transduction ; Transferrin/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-08-25
    Description: The mechanochemical protein dynamin is the prototype of the dynamin superfamily of large GTPases, which shape and remodel membranes in diverse cellular processes. Dynamin forms predominantly tetramers in the cytosol, which oligomerize at the neck of clathrin-coated vesicles to mediate constriction and subsequent scission of the membrane. Previous studies have described the architecture of dynamin dimers, but the molecular determinants for dynamin assembly and its regulation have remained unclear. Here we present the crystal structure of the human dynamin tetramer in the nucleotide-free state. Combining structural data with mutational studies, oligomerization measurements and Markov state models of molecular dynamics simulations, we suggest a mechanism by which oligomerization of dynamin is linked to the release of intramolecular autoinhibitory interactions. We elucidate how mutations that interfere with tetramer formation and autoinhibition can lead to the congenital muscle disorders Charcot-Marie-Tooth neuropathy and centronuclear myopathy, respectively. Notably, the bent shape of the tetramer explains how dynamin assembles into a right-handed helical oligomer of defined diameter, which has direct implications for its function in membrane constriction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reubold, Thomas F -- Faelber, Katja -- Plattner, Nuria -- Posor, York -- Ketel, Katharina -- Curth, Ute -- Schlegel, Jeanette -- Anand, Roopsee -- Manstein, Dietmar J -- Noe, Frank -- Haucke, Volker -- Daumke, Oliver -- Eschenburg, Susanne -- England -- Nature. 2015 Sep 17;525(7569):404-8. doi: 10.1038/nature14880. Epub 2015 Aug 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut fur Biophysikalische Chemie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. ; Max-Delbruck-Centrum fur Molekulare Medizin, Kristallographie, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Institut fur Mathematik, Freie Universitat Berlin, Arnimallee 6, 14195 Berlin, Germany. ; Leibniz-Institut fur Molekulare Pharmakologie, Robert-Rossle-Strasse 10, 13125 Berlin, Germany. ; Forschungseinrichtung Strukturanalyse, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. ; Institut fur Chemie und Biochemie, Freie Universitat Berlin, Takustrasse 6, 14195 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26302298" target="_blank"〉PubMed〈/a〉
    Keywords: Charcot-Marie-Tooth Disease ; Crystallography, X-Ray ; Dynamins/*antagonists & inhibitors/*chemistry/genetics/metabolism ; Humans ; Markov Chains ; Models, Molecular ; Molecular Dynamics Simulation ; Mutant Proteins/antagonists & inhibitors/chemistry/genetics/metabolism ; Mutation/genetics ; Myopathies, Structural, Congenital ; Nucleotides ; *Protein Multimerization/genetics ; Structure-Activity Relationship
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2013-07-05
    Description: Phosphoinositides serve crucial roles in cell physiology, ranging from cell signalling to membrane traffic. Among the seven eukaryotic phosphoinositides the best studied species is phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), which is concentrated at the plasma membrane where, among other functions, it is required for the nucleation of endocytic clathrin-coated pits. No phosphatidylinositol other than PI(4,5)P2 has been implicated in clathrin-mediated endocytosis, whereas the subsequent endosomal stages of the endocytic pathway are dominated by phosphatidylinositol-3-phosphates(PI(3)P). How phosphatidylinositol conversion from PI(4,5)P2-positive endocytic intermediates to PI(3)P-containing endosomes is achieved is unclear. Here we show that formation of phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) by class II phosphatidylinositol-3-kinase C2alpha (PI(3)K C2alpha) spatiotemporally controls clathrin-mediated endocytosis. Depletion of PI(3,4)P2 or PI(3)K C2alpha impairs the maturation of late-stage clathrin-coated pits before fission. Timed formation of PI(3,4)P2 by PI(3)K C2alpha is required for selective enrichment of the BAR domain protein SNX9 at late-stage endocytic intermediates. These findings provide a mechanistic framework for the role of PI(3,4)P2 in endocytosis and unravel a novel discrete function of PI(3,4)P2 in a central cell physiological process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Posor, York -- Eichhorn-Gruenig, Marielle -- Puchkov, Dmytro -- Schoneberg, Johannes -- Ullrich, Alexander -- Lampe, Andre -- Muller, Rainer -- Zarbakhsh, Sirus -- Gulluni, Federico -- Hirsch, Emilio -- Krauss, Michael -- Schultz, Carsten -- Schmoranzer, Jan -- Noe, Frank -- Haucke, Volker -- England -- Nature. 2013 Jul 11;499(7457):233-7. doi: 10.1038/nature12360. Epub 2013 Jul 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz Institut fur Molekulare Pharmakologie & Freie Universitat Berlin, Robert-Roessle-Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23823722" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; COS Cells ; Cercopithecus aethiops ; Class II Phosphatidylinositol 3-Kinases/metabolism ; Clathrin-Coated Vesicles/metabolism ; *Endocytosis ; HEK293 Cells ; HeLa Cells ; Humans ; Molecular Sequence Data ; Phosphatidylinositol Phosphates/*metabolism ; Phosphoric Monoester Hydrolases/metabolism ; Sorting Nexins/metabolism ; Time Factors
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2016-01-14
    Description: Phosphoinositides are a minor class of short-lived membrane phospholipids that serve crucial functions in cell physiology ranging from cell signalling and motility to their role as signposts of compartmental membrane identity. Phosphoinositide 4-phosphates such as phosphatidylinositol 4-phosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) are concentrated at the plasma membrane, on secretory organelles, and on lysosomes, whereas phosphoinositide 3-phosphates, most notably phosphatidylinositol 3-phosphate (PI(3)P), are a hallmark of the endosomal system. Directional membrane traffic between endosomal and secretory compartments, although inherently complex, therefore requires regulated phosphoinositide conversion. The molecular mechanism underlying this conversion of phosphoinositide identity during cargo exit from endosomes by exocytosis is unknown. Here we report that surface delivery of endosomal cargo requires hydrolysis of PI(3)P by the phosphatidylinositol 3-phosphatase MTM1, an enzyme whose loss of function leads to X-linked centronuclear myopathy (also called myotubular myopathy) in humans. Removal of endosomal PI(3)P by MTM1 is accompanied by phosphatidylinositol 4-kinase-2alpha (PI4K2alpha)-dependent generation of PI(4)P and recruitment of the exocyst tethering complex to enable membrane fusion. Our data establish a mechanism for phosphoinositide conversion from PI(3)P to PI(4)P at endosomes en route to the plasma membrane and suggest that defective phosphoinositide conversion at endosomes underlies X-linked centronuclear myopathy caused by mutation of MTM1 in humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ketel, Katharina -- Krauss, Michael -- Nicot, Anne-Sophie -- Puchkov, Dmytro -- Wieffer, Marnix -- Muller, Rainer -- Subramanian, Devaraj -- Schultz, Carsten -- Laporte, Jocelyn -- Haucke, Volker -- England -- Nature. 2016 Jan 21;529(7586):408-12. doi: 10.1038/nature16516. Epub 2016 Jan 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz-Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany. ; Department of Translational Medicine and Neurogenetics, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), INSERM U964, CNRS UMR7104, Strasbourg University, 67404 Illkirch, France. ; Freie Universitat Berlin, Faculty of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany. ; European Molecular Biology Laboratory (EMBL), Cell Biology and Biophysics Unit, 69117 Heidelberg, Germany. ; NeuroCure Cluster of Excellence, Charite Universitatsmedizin Berlin, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26760201" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2014-12-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Haucke, Volker -- England -- Nature. 2015 Jan 22;517(7535):446-7. doi: 10.1038/nature14081. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Leibniz Institut fur Molekulare Pharmakologie, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517097" target="_blank"〉PubMed〈/a〉
    Keywords: Acyltransferases/*metabolism ; Animals ; Cell Membrane/*metabolism ; *Endocytosis ; Humans
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 8
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  • 10
    Publication Date: 2004-01-15
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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