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Integrating molecular and network biology to decode endocytosis

Nature volume 448, pages 883–888 (2007)Cite this article

Abstract

The strength of network biology lies in its ability to derive cell biological information without a priori mechanistic or molecular knowledge. It is shown here how a careful understanding of a given biological pathway can refine an interactome approach. This permits the elucidation of additional design principles and of spatio-temporal dynamics behind pathways, and aids in experimental design and interpretation.

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Figure 1: Clathrin-coated vesicle formation: molecular detail versus a network view.
Figure 2: Structural organization of the hubs in CME.
Figure 3: The steps of synaptic vesicle CCV formation.

References

  1. Kirchhausen, T. Clathrin. Annu. Rev. Biochem. 69, 699–727 (2000)

    Article  CAS  Google Scholar 

  2. Marsh, M. & McMahon, H. T. The structural era of endocytosis. Science 285, 215–220 (1999)

    Article  CAS  Google Scholar 

  3. Perry, M. M. & Gilbert, A. B. Yolk transport in the ovarian follicle of the hen (Gallus domesticus): lipoprotein-like particles at the periphery of the oocyte in the rapid growth phase. J. Cell Sci. 39, 257–272 (1979)

    CAS  PubMed  Google Scholar 

  4. Marsh, M. & Helenius, A. Virus entry: open sesame. Cell 124, 729–740 (2006)

    Article  CAS  Google Scholar 

  5. Brodin, L., Low, P. & Shupliakov, O. Sequential steps in clathrin-mediated synaptic vesicle endocytosis. Curr. Opin. Neurobiol. 10, 312–320 (2000)

    Article  CAS  Google Scholar 

  6. Schmid, E. M. et al. Role of the AP2 β-appendage hub in recruiting partners for CCV assembly. PLoS Biol. 4, e262 (2006)

    Article  Google Scholar 

  7. Owen, D. J. et al. A structural explanation for the binding of multiple ligands by the α-adaptin appendage domain. Cell 97, 805–815 (1999)

    Article  CAS  Google Scholar 

  8. Owen, D. J., Vallis, Y., Pearse, B. M., McMahon, H. T. & Evans, P. R. The structure and function of the β2-adaptin appendage domain. EMBO J. 19, 4216–4227 (2000)

    Article  CAS  Google Scholar 

  9. Blondeau, F. et al. Tandem MS analysis of brain CCVs reveals their critical involvement in synaptic vesicle recycling. Proc. Natl Acad. Sci. USA 101, 3833–3838 (2004)

    Article  ADS  CAS  Google Scholar 

  10. Praefcke, G. J. et al. Evolving nature of the AP2 α-appendage hub during CCV endocytosis. EMBO J. 23, 4371–4383 (2004)

    Article  CAS  Google Scholar 

  11. Mishra, S. K. et al. Dual engagement regulation of protein interactions with the AP-2 adaptor α appendage. J. Biol. Chem. 279, 46191–46203 (2004)

    Article  CAS  Google Scholar 

  12. Edeling, M. A. et al. Molecular switches involving the AP-2 β2 appendage regulate endocytic cargo selection and clathrin coat assembly. Dev. Cell 10, 329–342 (2006)

    Article  CAS  Google Scholar 

  13. Barabasi, A. L. & Oltvai, Z. N. Network biology: understanding the cell's functional organization. Nature Rev. Genet. 5, 101–113 (2004)

    Article  CAS  Google Scholar 

  14. Alon, U. Biological networks: the tinkerer as an engineer. Science 301, 1866–1867 (2003)

    Article  ADS  CAS  Google Scholar 

  15. Albert, R. Scale-free networks in cell biology. J. Cell Sci. 118, 4947–4957 (2005)

    Article  CAS  Google Scholar 

  16. Gavin, A. C. et al. Proteome survey reveals modularity of the yeast cell machinery. Nature 440, 631–636 (2006)

    Article  ADS  CAS  Google Scholar 

  17. Hartwell, L. H., Hopfield, J. J., Leibler, S. & Murray, A. W. From molecular to modular cell biology. Nature 402, (suppl.)C47–C52 (1999)

    Article  CAS  Google Scholar 

  18. Yarar, D., Waterman-Storer, C. M. & Schmid, S. L. A dynamic actin cytoskeleton functions at multiple stages of clathrin-mediated endocytosis. Mol. Biol. Cell 16, 964–975 (2005)

    Article  CAS  Google Scholar 

  19. Merrifield, C. J., Feldman, M. E., Wan, L. & Almers, W. Imaging actin and dynamin recruitment during invagination of single clathrin-coated pits. Nature Cell Biol. 4, 691–698 (2002)

    Article  CAS  Google Scholar 

  20. Kaksonen, M., Toret, C. P. & Drubin, D. G. A modular design for the clathrin- and actin-mediated endocytosis machinery. Cell 123, 305–320 (2005)

    Article  CAS  Google Scholar 

  21. Ekman, D., Light, S., Bjorklund, A. K. & Elofsson, A. What properties characterize the hub proteins of the protein–protein interaction network of Saccharomyces cerevisiae?. Genome Biol. 7, R45 (2006)

    Article  Google Scholar 

  22. Han, J. D. et al. Evidence for dynamically organized modularity in the yeast protein–protein interaction network. Nature 430, 88–93 (2004)

    Article  ADS  CAS  Google Scholar 

  23. McMahon, H. T. & Mills, I. G. COP and CCV budding: different pathways, common approaches. Curr. Opin. Cell Biol. 16, 379–391 (2004)

    Article  CAS  Google Scholar 

  24. Brett, T. J. & Traub, L. M. Molecular structures of coat and coat-associated proteins: function follows form. Curr. Opin. Cell Biol. 18, 395–406 (2006)

    Article  CAS  Google Scholar 

  25. Niethammer, P. et al. Discrete states of a protein interaction network govern interphase and mitotic microtubule dynamics. PLoS Biol. 5, e29 (2007)

    Article  Google Scholar 

  26. Slepnev, V. I. & De Camilli, P. Accessory factors in clathrin-dependent synaptic vesicle endocytosis. Nature Rev. Neurosci. 1, 161–172 (2000)

    Article  CAS  Google Scholar 

  27. Honing, S. et al. Phosphatidylinositol-(4,5)-bisphosphate regulates sorting signal recognition by the clathrin-associated adaptor complex AP2. Mol. Cell 18, 519–531 (2005)

    Article  Google Scholar 

  28. Jeong, H., Mason, S. P., Barabasi, A. L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001)

    Article  ADS  CAS  Google Scholar 

  29. Motley, A., Bright, N. A., Seaman, M. N. & Robinson, M. S. Clathrin-mediated endocytosis in AP-2-depleted cells. J. Cell Biol. 162, 909–918 (2003)

    Article  CAS  Google Scholar 

  30. Kruchten, A. E. & McNiven, M. A. Dynamin as a mover and pincher during cell migration and invasion. J. Cell Sci. 119, 1683–1690 (2006)

    Article  CAS  Google Scholar 

  31. Wienke, D. C., Knetsch, M. L., Neuhaus, E. M., Reedy, M. C. & Manstein, D. J. Disruption of a dynamin homologue affects endocytosis, organelle morphology, and cytokinesis in Dictyostelium discoideum. Mol. Biol. Cell 10, 225–243 (1999)

    Article  CAS  Google Scholar 

  32. Praefcke, G. J. & McMahon, H. T. The dynamin superfamily: universal membrane tubulation and fission molecules? Nature Rev. Mol. Cell Biol. 5, 133–147 (2004)

    Article  CAS  Google Scholar 

  33. Hinrichsen, L., Harborth, J., Andrees, L., Weber, K. & Ungewickell, E. J. Effect of clathrin heavy chain- and α-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells. J. Biol. Chem. 278, 45160–45170 (2003)

    Article  CAS  Google Scholar 

  34. Maslov, S. & Sneppen, K. Specificity and stability in topology of protein networks. Science 296, 910–913 (2002)

    Article  ADS  CAS  Google Scholar 

  35. Shenoy, S. K. & Lefkowitz, R. J. Seven-transmembrane receptor signaling through β-arrestin. Sci. STKE 2005, cm10 (2005)

    PubMed  Google Scholar 

  36. Puthenveedu, M. A. & von Zastrow, M. Cargo regulates clathrin-coated pit dynamics. Cell 127, 113–124 (2006)

    Article  CAS  Google Scholar 

  37. Marks, B. & McMahon, H. T. Calcium triggers calcineurin-dependent synaptic vesicle recycling in mammalian nerve terminals. Curr. Biol. 8, 740–749 (1998)

    Article  CAS  Google Scholar 

  38. Slepnev, V. I., Ochoa, G. C., Butler, M. H., Grabs, D. & De Camilli, P. Role of phosphorylation in regulation of the assembly of endocytic coat complexes. Science 281, 821–824 (1998)

    Article  ADS  CAS  Google Scholar 

  39. Prachumwat, A. & Li, W. H. Protein function, connectivity, and duplicability in yeast. Mol. Biol. Evol. 23, 30–39 (2006)

    Article  CAS  Google Scholar 

  40. Mills, I. G. et al. EpsinR: an AP1/clathrin interacting protein involved in vesicle trafficking. J. Cell Biol. 160, 213–222 (2003)

    Article  Google Scholar 

  41. Schubert, W. et al. Analyzing proteome topology and function by automated multidimensional fluorescence microscopy. Nature Biotechnol. 24, 1270–1278 (2006)

    Article  CAS  Google Scholar 

  42. Smith, C. J., Grigorieff, N. & Pearse, B. M. Clathrin coats at 21 Å resolution: a cellular assembly designed to recycle multiple membrane receptors. EMBO J. 17, 4943–4953 (1998)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all those who contributed; M. Ford, G. Doherty and R. Mittal for many ideas that go well beyond what is written; P. Evans and M. Ford for their help with the figures; M. Babu for giving us an interest in network biology and informing that interest; and the many who have read and critically commented on the manuscript.

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  1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK,

    Eva M. Schmid & Harvey T. McMahon

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  1. Eva M. Schmid
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Correspondence to Harvey T. McMahon.

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This file contains Supplementary Notes, Supplementary Figures 1-4 with Legends and Supplementary Tables 1-2 with Legends. (PDF 1915 kb)

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Schmid, E., McMahon, H. Integrating molecular and network biology to decode endocytosis. Nature 448, 883–888 (2007). https://doi.org/10.1038/nature06031

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