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BBB-seminar: Jaakko Saraste

Mapping novel transport routes to the cell surface

Jaakko Saraste, Department of Biomedicine, University of Bergen

About one third of the proteins encoded by eukaryotic genomes are synthesized on endoplasmic reticulum (ER)-bound ribosomes. The secretory pathway sorts and delivers the ER-derived biosynthetic products – not just proteins, but also various lipids and sterols – to the extracellular space, the plasma membrane (PM), or different compartments of the endomembrane system. In addition to the classical ER-Golgi-PM pathway, there is emerging evidence for alternative routes to the cell surface that bypass the Golgi apparatus, the center for post-synthetic processing of the transported molecules. The operation of such pathways could be coupled to various physiological conditions that all involve extensive PM growth, including cell polarization, migration, neurite outgrowth, phagocytosis and mitosis. However, the mechanisms of these non-classical routes remain poorly understood (1,2).

In contrast to the prevailing views, our recent work has shown that the intermediate compartment (IC) at the ER-Golgi boundary constitutes a stable tubular network, which maintains its dynamics under conditions that lead to Golgi disassembly (cell division, Brefeldin A-treatment). As a result, we obtained evidence for two bidirectional Golgi bypass pathways to the PM: i) a direct route from peripheral IC elements that participates in biosynthetic cholesterol trafficking (3), and ii) a route from centrosome-associated IC elements via the endosomal system (4). Besides explaining how molecules can reach the cell surface in a Golgi-independent manner, these studies identify a previously unrecognized pericentrosomal membrane system, which must be taken into account when considering the functional organization of the secretory pathways in different cell types.

References:
1. Marie, M., Sannerud, R., Dale, H.A. and Saraste, J. (2008). Take the ‘A’ train: On fast tracks to the cell surface. Cellular and Molecular Life Sciences. 65, 2859-74.
2. Nickel, W. and Rabouille, C. (2009). Mechanisms of regulated, unconventional protein secretion. Nature Reviews in Molecular Cell Biology. Published online 24 December 2008.
3. Sannerud, R., Marie, M., Nizak, C., Dale, H.A., Perez, F., Goud, B., and Saraste, J. (2006). Rab1 defines a novel pathway connecting the pre-Golgi intermediate compartment with the cell periphery. Molecular Biology of the Cell 17, 1514-26.
4. Marie, M., Dale, H.A., Sannerud, R. and Saraste, J. (2008). The function of the intermediate compartment in pre-Golgi trafficking involves its stable connection with the centrosome. Submitted.


Chair: Jan Haavik , Department of Biomedicine