David D. Sabatini, M.D., Ph.D.
Frederic L. Ehrman Professor, Department of Cell Biology, New York University School of Medicine
CITATION OF MOST IMPORTANT ACCOMPLISHMENT:
David Sabatini provided the initial evidence that led to his formulation, together with Gunter Blobel, of the "signal hypothesis". His work opened the field of intracellular protein trafficking, to which he made numerous contributions, including his discovery of the polarized budding of viruses in epithelial cells.
David Sabatini has made many seminal contributions to cell biology. These began with his introduction of the glutaraldehyde fixation procedure, which revolutionized the field of biological electron microscopy by permitting cytochemical studies at the EM level, and providing much more refined images of subcellular organelles, as well as allowing the discovery of new ones-most notably components of the cytoskeleton. His studies on membrane bound ribosomes led to his discovery of the process of cotranslational translocation of polypeptides across the ER membrane, and represents the basis for the signal hypothesis, which he proposed together with Gunter Blobel. Sabatini's work also led him to the first proposal of the existence of a channel within the ribosome in which the nascent polypeptide grows, that becomes continuous with a pore through the ER membrane in an arrangement that allows for the vectorial discharge of the polypeptide into the ER lumen. His work on the polarity of epithelial cells introduced the now widely adopted MDCK cell line for studies of the biogenesis of the plasma membrane and epithelial cell polarity. The discovery in his laboratory of the polarized budding of envelope virus from epithelial cells and the intracellular sorting of viral envelope glycoproteins to the appropriate cell surface domains, offered a powerful new experimental system that has advanced the field of protein traffic. His laboratory continues to increase our knowledge of diverse aspects of protein traffic, including the formation of transport vesicles in the Golgi apparatus and the regulation of traffic within the endocytic and recycling pathways.
1. D.D. Sabatini, K. Bensch, and R. Barrnett. (1963) Cytochemistry and electron microscopy. The preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation . J. Cell Biol . 17 :19-59.
2. D.D. Sabatini, Y. Tashiro, and G.E. Palade. (1966) On the attachment of ribosomes to microsomal membranes. J. Mol. Biol . 19 :503-524.
3. C. Redman and D.D. Sabatini. (1966) Vectorial discharge of peptides released by puromycin from attached ribosomes. Proc. Natl. Acad. Sci. USA 56 :608-615.
4. D.D. Sabatini and G. Blobel. (1970) Controlled proteolysis of nascent polypeptides in rat liver cell fractions. II. Location of the polypeptides in rough microsomes. J. Cell Biol. 45 :146-157.
5. G. Blobel and D.D. Sabatini. (1971) Ribosome-membrane interactions in eukaryotic cells. In: Biomembranes, Vol. 2, L.A. Manson, ed., Plenum Publishing Corp., New York , pps. 193-195.
6. M. Cereijido, E.S. Robbins. C.A. Rotunno, W.J. Dolan, and D.D. Sabatini. (1978) Polarized monolayers formed by epithelial cells on a permeable and translucent support. J. Cell. Biol . 77 :853-880.
7. E. Rodriguez-Boulan and D.D. Sabatini. (1979) Asymmetric budding of viruses in epithelial cells in culture: A model system for study of epithelial polarity. Proc. Natl. Acad. Sci . USA 76 :5071-5075.
8. M.J. Rindler, I.E. Ivanov, H. Plesken, and D.D. Sabatini. (1985) Polarized delivery of viral glycoproteins to the apical and basolateral membranes of MDCK cells infected with temperature sensitive viruses. J. Cell Biol. 100 :136-151.
9. J.-P. Simon, I.E. Ivanov, B. Shopsin, D. Hersh, M. Adesnik, and D.D. Sabatini. (1996) The in vitro generation of post golgi vesicles carrying viral envelope glycoproteins requires an ARF-like GTP-binding protein and a protein kinase C associated with the golgi apparatus. J. Biol. Chem. 271 :16952-16961.
10. J. Zeng, M. Ren, D. Gravotta, C. De Lemos-Chiarandini, P. Tempt, H. Erdjument-Bromage, M. Lui, G. Xu, T.H. Shen, T. Morimoto, M. Adesnik, and D.D. Sabatini. (1999). Identification of a putative effector protein for rab11 that participates in transferrin recycling. Proc. Natl. Acad. Sci. USA. 96 :2840-2845.
11. M. Ren, G. Xu, J. Zeng, C. De Lemos-Chiarandini, M. Adesnik, and D.D. Sabatini. (1998). Hydrolysis of GTP on rab11 is required for the direct delivery of transferrin from the pericentriolar recycling compartment to the cell surface but not from sorting endosomes. Proc. Natl. Acad. Sci . USA 95 :6187-6192.
12. J.-P. Simon, T. Morimoto, V.A. Bankaitis, T.A. Gottlieb, I.E. Ivanov, M. Adesnik, and D.D. Sabatini. (1998). An essential role for the phosphatidylinositol transfer protein in the scission of the coatomer-coated vesicles from the TGN. Proc. Natl. Acad. Sci . USA. 95 :11181-11186.
13. J. Zeng, M. Ren, D. Gravotta, C. De Lemos-Chiarandini, P. Tempt, H. Erdjument-Bromage, M. Lui, G. Xu, T.H. Shen, T. Morimoto, M. Adesnik, and D.D. Sabatini. (1999). Identification of a putative effector protein for rab11 that participates in transferrin recycling. Proc. Natl. Acad. Sci. USA. 96 :2840-2845.
14. H.P. Harding, H. Zeng, Y. Zhang, R. Jungries, P. Chung, H. Plesken, D.D. Sabatini and D. Ron. (2001) Diabetes mellitus and exocrine pancreatic dysfunction in Perk-/- mice reveals a role for translational control in secretory cell survival. Mol. Cell , 7 :1153-1163.
15. Y. Chen, X. Guo, F. Deng, F. Liang, W. Sun, M. Ren, T. Izumi, D.D. Sabatini, T. Sun, and G. Kreibich. (2003). Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes. Proc. Natl. Acad. Sci . Vol: 100 No. 24 pps. 14012-14017.