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| Mitotic regulation of ER-to-Golgi membrane traffic | |||||||||||||
The first membrane trafficking step in mammalian cells is the export of secretory cargo from the ER 1. This step defines the downstream architecture and composition of many other organelles. Significantly, arrest of ER export is observed during mitosis 2, 3. This is a key component of the mechanisms that ensure accurate inheritance of organelles between daughter cells. Little is known of the mechanism underlying this mitotic inhibition but it has key implications for cell division itself as well as for the organization of mammalian cells, notably the structure and function of the Golgi apparatus. It has been suggested that the ER export event is a critical determinant of Golgi biogenesis 4, probably through populating a template of matrix proteins 5. Understanding the mechanisms by which ER export is inhibited on entry into mitosis and restarted on exit from mitosis are therefore central to our understanding of cellular organization and function. This project will address the fundamental principles of cellular organization throughout the cell cycle. The ER/Golgi interface displays a characteristic architecture in mammalian cells with ER exit sites distributed throughout the cytoplasm. The ER export event is spatially organized into discrete domains on the ER membrane called ER exit sites. We propose to investigate the organization of the early secretory pathway during the progression of mammalian cells through mitosis to define the spatial and temporal control of ER export activity. The project will involve a considerable amount of live cell imaging using the equipment and experience within the Stephens lab as well as the exceptional facilities within Wolfson Bioimaging Facility. The aim of this project is to identify the mechanisms underlying mitotic regulation of early secretory pathway function and how this dictates the downstream organization of daughter cells on exit from mitosis. For further information see: http://www.bristol.ac.uk/biochemistry/stephens/index.html 1. Hughes, H. & Stephens, D.J. Assembly, organization, and function of the COPII coat. Histochem. Cell Biol. 129, 129-151 (2008) 2. Wei, J.H. & Seemann, J. Mitotic division of the mammalian Golgi apparatus. Semin Cell Dev Biol (2009) 3. Stephens, D.J. De novo formation, fusion and fission of mammalian COPII-coated endoplasmic reticulum exit sites. EMBO rep. 4, 210-217 (2003) 4. Zaal, K.J. et al. Golgi membranes are absorbed into and reemerge from the ER during mitosis. Cell 99, 589-601 (1999) 5. Seemann, J., Pypaert, M., Taguchi, T., Malsam, J. & Warren, G. Partitioning of the matrix fraction of the Golgi apparatus during mitosis in animal cells. Science 295, 848-851 (2002) |
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