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83 From synthetic endosomes to a systems analysis of endocytosis Marino Zerial 1 , Takeshi Ohya 1 , Marta Miaczynska 1 , Claudio Collinet 1 , Martin Stöter 1 , Nikolay Samusik 1 , Giovanni Marsico 1 , Eugenio Fava 1 , Marc Bickle 1 , Yannis Kalaidzidis 1 . Max Planck Institute of Molecular Cell Biology and Genetics, MPI-CBG, Dresden, Germany 1 Abstract: Endocytosis is an essential process serving multiple key cellular functions, such as nutrient uptake, signal transduction, and defence against pathogens. Rab GTPases act as membrane organizers, specifying the structural and functional identity of endosomes. Rab proteins occupy distinct membrane territories or “Rab-domains” linked by a binary switch system consisting of divalent effectors, GEFs and GAPs that sequentially activate and repress Rab GTPases along the pathway. Using a biochemical approach, we reconstituted the Rab5 GTPase, its key regulators and effectors together with early endosomal SNAREs into proteo-liposomes using a set of 17 recombinant proteins. These vesicles behave like “synthetic” endosomes, fusing with purified early endosomes or with each other in vitro. Our results suggest that Rab effectors together with SNAREs constitute the core machinery of the membrane tethering and fusion process. To elucidate the machinery underlying endosome function and endocytosis further, we undertook a systems biology analysis. We systematically profiled the activity of human genes with respect to Transferrin and EGF endocytosis by performing an image-based RNAi screening of HeLa cells in cooperation with the HT-TDS, the screening facility of the MPI-CBG. The genes were identified on the basis of a multi-parametric analysis quantitatively measuring uptake and intracellular cargo distribution. We uncovered novel regulators of endocytosis and endosome trafficking, including many signalling pathways (e.g. Wnt, Integrin, TGF-β, and Notch). A systems analysis by Bayesian networks further uncovered design principles regulating the number, size, concentration of cargo and intracellular position of endosomes.
Author Index - A- Abay, S., 33 Acharya, S., 47 Akbar, M. A., 1 Alpadi, K., 2 Amaral, M. D., 56 Andersson, S., 70 Aoh, Q., 3 Apodaca, G. L., 52 -B- Bard, F., 4, 19 Barr, F. A., 5 Bazan, F., 27 Bazan, J. F., 44 Beck-Sickinger, A. G., 77 Bernhagen, J., 63 Bharucha, N., 21 Bickle, M., 83 Bonifacino, J., 11 Bonifacino, J. S., 61 Bostina, M., 64 Boulanger, M., 6 Boulant, S., 7 Bradbury, N. A., 8 Brewer, D. N.., 43 Bridges, R. J., 8 Brodsky, F. M., 9 Burd, C., 10 -C- Carr, C. M., 43 Carvajal-Gonzalez, J. M., 11 Chait, B. T., 15 Champagne, C., 6 Chappie, J. S., 62 Chen, D., 41 Chesley, P., 51 Chetrit, D., 12 Chia, J., 19 Clarke, I., 41 Colabella, H., 8 Coleman, J., 20, 48 Collinet, C., 83 Cooper, S. T., 13 Copic, A., 32 Costantino, S., 38 Cristea, I. M., 15 Cullen, P. J., 1, 7 -D- Dacks, J., 24 Dalgalan, D., 80 Danson, C., 14, 72 Dargemont, C., 15 Davidson, M. W., 34 De Matteis, M., 74 Delevoye, C., 61 Devos, D. P., 15 Di Tullio, G., 74 DiAntonio, A., 30 Diaz, F., 11 Dippold, H. C., 18 Dokudovskaya, S., 15 Dumaresq-Doiron, K., 28 Duncan, M., 3 Dyda, F., 62 -E- Ehrlich, M., 12 Emr, S. D., 16 Engel, S., 23 English, A. R., 17 Enrich, C., 55 Erlmann, P., 58 Esaki, M., 21 Evesson, F. J., 13
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October 28 - October 31, 2010 Bioch
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Symposium Agenda Thursday, October
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12:10 p.m. - 4:00 p.m. Lunch and Fr
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4:50 p.m. - 5:00 p.m. Discussion 5:
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Poster Presentations Last Names A -
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The Role of Ceroid Lipofuscinosis N
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A novel Golgi-localized protein inv
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2 The dynamics of SNARE complexes i
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4 Significant divergence in mammali
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6 The Tumoricidal Action of the Ade
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8 LMTK2 Regulates CFTR Recycling in
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10 Sorting in the Golgi Apparatus C
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12 Negative regulation of the endoc
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14 Mechanistic details of sorting n
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16 An ESCRTs View of Receptor Endoc
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18 GOLPH3 Bridges PtdIns(4)P and My
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20 Novel fluorescent probes to stud
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22 Regulation of Ligand-Independent
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24 A Fifth Adaptor Protein Complex
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26 CATCHR-Family Tethering Complexe
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28 Rab7 localization and activity a
Page 43 and 44: 30 The Drosophila Golgi transmembra
Page 45 and 46: 33 Cbl Amino Acids at a Putative Di
Page 47 and 48: 35 The role of COG subcomplexes in
Page 49 and 50: 37 Mechanism of secretory cargo sor
Page 51 and 52: 39 Understanding the mechanism of G
Page 53 and 54: 41 Mechanisms for selective activat
Page 55 and 56: 44 A novel coat complex traffics me
Page 57 and 58: 46 Membrane trafficking in cytokine
Page 59 and 60: 48 Phosphatidylinositol 4-phosphate
Page 61 and 62: 50 Control of Golgi function by Rab
Page 63 and 64: 52 Adenosine mediated modulation of
Page 65 and 66: 54 Syp1 regulation of actin polymer
Page 67 and 68: 56 Rap1A: A Novel Interactor Involv
Page 69 and 70: 58 Ctage5 is involved in the endopl
Page 71 and 72: 60 A vesicle carrier that mediates
Page 73 and 74: 62 Structural Insights into Dynamin
Page 75 and 76: 64 Identification and interaction m
Page 77 and 78: 66 hRME-6, a rab5GEF that integrate
Page 79 and 80: 68 Assembly of caveolin-1 and cavin
Page 81 and 82: 70 Opposing roles of Annexin A1 and
Page 83 and 84: 72 The role of SNX-BAR proteins in
Page 85 and 86: 74 TRAPP is required for ER exit of
Page 87 and 88: 76 A structural analysis of the ER
Page 89 and 90: 78 Cell cycle-regulated Golgi stack
Page 91 and 92: 80 Rab 14 regulates tight junction
Page 93: 82 Dissecting the roles of O-glycos
Page 97 and 98: Marsico, G., 83 Mattera, R., 11 Max
Page 99: 2011 ASBMB Special Symposia Series
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