David D.

Sabatini
David Domingo Sabatini is an Argentine-American
cell biologist and the Frederick L. Ehrman Professor David Domingo Sabatini
Emeritus of Cell Biology in the Department of Cell Alma mater National University of the
Biology at New York University School of Litoral (MD)
Medicine,[2] which he chaired from 1972 to 2011. Rockefeller University (PhD)
Sabatini's major research interests have been on the
Awards E.B. Wilson Medal (1986)
mechanisms responsible for the structural complexity
of the eukaryotic cell. Throughout his career, Sabatini Scientific career
has been recognized for his efforts in promoting Fields Cell biology
science in Latin America.[3] Institutions Rockefeller University, New
York University
Thesis (1966)
Early life and education Notable Enrique Rodriguez-Boulan[1]
students
Sabatini is a native of Argentina, and attended medical
school in Rosario at the National University of the
Litoral. He began his research career at the University of Buenos Aires, in the laboratory of Eduardo De
Robertis, a founder of modern cell biology, where he developed skills in electron microscopy. In 1961, as
a Rockefeller Foundation fellow, he traveled to the United States, first for a six-month stint at Yale
University to work with histochemist Russell Barnett, and then to work with George Palade and Philip
Siekevitz at the Rockefeller University. Whilst at Yale he introduced glutaraldehyde as a fixative for
electron microscopy and cytochemistry.[4] After a year as a postdoctoral fellow at Rockefeller, Sabatini
entered the Rockefeller graduate program from which he received a PhD in 1966 for studies on protein
translation by ribosomes attached to endoplasmic reticulum membranes.[5][6]

Research overview
Sabatini's research has focused on the mechanisms by which proteins are targeted to different organelles
within the cell. His early work studied co-translational targeting of ribosomes to the endoplasmic
reticulum and helped establish the hypothesis that signal peptides direct protein traffic to cellular
compartments.[7] He later focused on trafficking from the Golgi apparatus to secretory vesicles and to the
plasma membrane and in particular the mechanisms that address membrane proteins to the different
surface domains of epithelial cells for which he employed viral infected epithelial monolayers.[8]

Academic career
After finishing his PhD, Sabatini joined the faculty at Rockefeller and in his own laboratory continued
studies on protein trafficking in the ER. With a group of young associates (Nica Borgese, Mark Adelman,
and Gert Kreibich), collaborating with Gunter Blobel, he continued research on the mechanism that
ensures the co-translational translocation and vectorial discharge of nascent polypeptides into and across
the endoplasmic reticulum membrane. In in vitro experiments they discovered that the microsomal
membrane protected the N-terminal portion of nascent polypeptides synthesized in membrane bound
ribosomes from proteolytic attack by exogenous enzymes.[9][10][11][12] These studies strongly implicated
the N-terminal portions of nascent polypeptides in establishing and maintaining the association of bound
ribosomes with ER membranes.

Largely based on these findings, in 1971 Blobel and Sabatini proposed a speculative model[13] that later
came to be known as the "signal hypothesis". For a discussion of the genesis and evolution of the signal
hypothesis see LaBonte, 2017[14] In the 1971 paper, Blobel and Sabatini proposed that “all mRNAs to be
translated on bound ribosomes have a common feature, such as several codons near their 5’ end, not
present in mRNAs which are to be translated on free ribosomes” and that “the resulting common
sequence of amino acids near the N-termini of the nascent chains, or a modification of it, would then be
recognized by a factor mediating the binding to the membrane." They proposed that "This binding factor
could be a soluble protein, which recognizes both a site on the large ribosomal subunit and a site on the
membrane.”[15] A decade later, Walter and Blobel demonstrated the existence of a Signal Recognition
Protein (SRP) that mediates the binding of the ribosome and the signal sequence within the nascent chain
to the membrane.[16][17] In 1982, a cognate receptor for the Signal Recognition Particle (SRP) was
discovered and characterized in the ER membrane.[18][19][20]

In 1972, Sabatini moved his laboratory to the New York University School of Medicine to become the
chair of the Department of Cell Biology,[21] where he assembled a group that focused on the study of
membrane and organelle biogenesis.[22] Initially, that work placed a primary emphasis on identifying
structural features of secretory, lysosomal[23] and integral membrane proteins[24] that are synthesized on
membrane bound ribosomes, address them to specific subcellular locations and determine their
disposition within a membrane.

In the late 1970s, in collaboration with Marcelino Cereijido[25] he introduced the now widely used
MDCK cell culture system for the study of epithelial cell polarity and together with Enrique Rodriguez-
Boulan reported the landmark discovery of the asymmetric budding of specific enveloped viruses from
the different surfaces of epithelial cells.[26][27]

Honors and awards

Sabatini was elected a fellow of the American Academy of Arts and Sciences in 1980[28] and became a
member of the U.S. National Academy of Sciences in 1985.[29] In 1986, together with Günter Blobel, he
received the E.B. Wilson Medal, the highest honor of the American Society of Cell Biology, of which he
was president in 1978-79.[30] He was selected to give the ASCB's Keith R. Porter Lecture in 1983.[31][32]

He is a member of the U.S. National Academy of Medicine, a member of the American Philosophical
Society,[33] and a foreign associate of the French Academy of Sciences. He was awarded the Charles
Leopold Mayer Prize (1986) and the Grande Médaille (2003) by the French Academy of Sciences, and in
2006 he was named a Chevalier de la Légion d’honneur.

Personal life
Sabatini's wife Zulema is also from Argentina and is a medical doctor specializing in pathology. The
couple's two sons are both current or former MD–PhD academic research scientists and Howard Hughes
Medical Institute investigators: Bernardo L. Sabatini is a neuroscientist at Harvard Medical School and
David M. Sabatini was a cell biologist at the Massachusetts Institute of Technology until he resigned in
2022.[34][35][36]

References
1. "Richard Lounsbery Foundation | Sabatini" (https://www.rlounsbery.org/sabatini).
2. "David D. Sabatini" (https://med.nyu.edu/faculty/david-d-sabatini). New York University.
Retrieved 5 April 2017.
3. Adesnik M. 2002. David Sabatini--a lifelong fascination with organelles. TRENDS in Cell
Biology. 12:347-49
4. Sabatini DD, Bensch K, Barrnett RJ. 1963. Cytochemistry and electron microscopy. The
preservation of cellular ultrastructure and enzymatic activity by aldehyde fixation. J. Cell
Biol. 17:19-58
5. Sabatini DD, Tashiro Y, Palade GE. 1966. On the attachment of ribosomes to microsomal
membranes. J. Mol. Biol. 19:503-24; Redman CM, Sabatini DD. 1966. Vectorial discharge of
peptides released by puromycin from attached ribosomes. Proc. Natl. Acad. Sci. USA
56:608-15
6. Redman CM, Sabatini DD. 1966. Vectorial discharge of peptides released by puromycin
from attached ribosomes. Proc. Natl. Acad. Sci. USA 56:608–15
7. Adesnik M. 2002. David Sabatini--a lifelong fascination with organelles. TRENDS in Cell
Biology. 12:347-49
8. IN AWE OF SUBCELLULAR COMPLEXITY: 50 Years of Trespassing Boundaries Within the
Cell David D. Sabatini Annual Review of Cell and Developmental Biology Vol. 21, 2005
9. Sabatini, D.D. and 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.
10. Blobel G. and Sabatini, D.D., (1970).Controlled proteolysis of nascent polypeptides in rat
liver cell fractions.I. Location of the polypeptides within ribosomes. J Cell Biol 45, 130-145
11. Adelman MR, Blobel G, Sabatini DD. 1973a. An improved cell fractionation procedure for
the preparation of rat liver membrane-bound ribosomes. J. Cell Biol. 56:191–205
12. Borgese N, Mok W, Kreibich G, Sabatini DD. 1974 Ribosomal-membrane interaction: in vitro
binding of ribosomes to microsomal membranes. J Mol Biol. 25:559-80(
13. G. Blobel, D.D. Sabatini,. Ribosome-membrane interaction in eukaryotic cells. 1971
Biomembranes, 2, 193–95
14. LaBonte, ML. 2017. Blobel and Sabatini's "Beautiful Idea": Visual Representations of the
Conception and Refinement of the Signal Hypothesis. J Hist Biol. 2017 50(4):797-833
15. G. Blobel, D.D. Sabatini,. Ribosome-membrane interactions in eukaryotic cells. 1971
Biomembranes, 2, 193–95
16. Walter P. & Blobel G., 1981, Translocation of proteins across the endoplasmic reticulum II,
Signal recognition protein(SRP) mediates the selective binding to microsomal membrane of
in-vitro- assembled polysomes synthesizing secretory proteins. J. Cell Biol. 91:551-56
17. Walter P. & Blobel G., 1983, Disassembly and reconstitution of signal recognition particle.
Cell 54: 525-33
18. Gilmore R. Blobel G. Walter P 1982a. Protein Translocation across the endoplasmic
reticulum I. Detection in the microsomal membrane of a receptor for the signal recognition
particle. J. Cell Biol. 95:463-69.
19. Gilmore R. Walter P. Blobel G. 1982b Protein translocation across the endoplasmic
reticulum II. Isolation and Characterization of the signal recognition particle receptor. J.Cell
Biol. 95:470-77
20. Meyer DI, Krause E, Dobberstein B.,1982). Secretory protein translocation across
membranes—the role of the “docking protein” Nature 297:647-50
21. Adesnik, Milton (July 2002). "David Sabatini – a lifelong fascination with organelles". Trends
in Cell Biology. 12 (7): 347–349. doi:10.1016/S0962-8924(02)02296-1 (https://doi.org/10.10
16%2FS0962-8924%2802%2902296-1). PMID 12185852 (https://pubmed.ncbi.nlm.nih.gov/
12185852).
22. Adesnik M. 2002. David Sabatini – a lifelong fascination with organelles. TRENDS in Cell
Biology. 12:347-49
23. Rosenfeld MG, Krebich G, Popov D, Kato, K Sabatini DD 1982, Biosynthesis of lysosomal
hydrolases: their synthesis in bound polysomes and the role of co- and post- translational
processing in determining their subcellular substitution J. Cell Biol. 93:135-43)
24. Monier, S, Van Luc P, Kreibich G, Sabatini DD, Adesnik M. (1988). Signals for the
incorporation and orientation of Cytochrome P450 in the endoplasmic reticulum
membranes. J Cell Biol. 107:457-70
25. Cereijido M, Robbins ES, Dolan WJ, Rotunno CA, Sabatini DD. 1978. Polarized monolayers
formed by epithelial cells on a permeable and transculent support. J. Cell Biol. 77:853-80
26. Rodriguez-Boulan ER, Sabatini DD. 1978. Asymmetric budding of viruses in epithelial
monolayers: a model system for study of epithelial polarity. Proc. Natl. Acad. Sci. USA
75:5071-75
27. Coming to Grips with Cell Surface polarity. Simons K. 2017 Nat Rev Mol Cell Biol. 2017
18:278
28. "David Sabatini" (https://www.amacad.org/content/system/search.aspx?s=david+sabatini).
American Academy of Arts and Sciences. Retrieved 5 April 2017.
29. "David Sabatini" (http://www.nasonline.org/member-directory/members/45760.html).
National Academy of Sciences Member Directory. Retrieved 5 April 2017.
30. "Past ASCB Officers" (https://web.archive.org/web/20170407053610/http://www.ascb.org/ab
out-ascb/past-ascb-officers/). American Society for Cell Biology. Archived from the original
(http://www.ascb.org/about-ascb/past-ascb-officers/) on 7 April 2017. Retrieved 6 April 2017.
31. "Keith R. Porter Lecture Award" (http://www.ascb.org/keith-r-porter-lecture-award/).
American Society for Cell Biology. Retrieved 7 April 2017.
32. "E.B. Wilson Medal" (http://www.ascb.org/e-b-wilson-medal/). American Society for Cell
Biology. Retrieved 7 April 2017.
33. "APS Member History" (https://search.amphilsoc.org/memhist/search?creator=David+D.+Sa
batini&title=&subject=&subdiv=&mem=&year=&year-max=&dead=&keyword=&smode=adva
nced). search.amphilsoc.org. Retrieved 2021-07-13.
34. Ware, Lauren (2013). "Science in their Blood" (http://www.hhmi.org/bulletin/spring-2013/scie
nce-their-blood). HHMI Bulletin. Howard Hughes Medical Institute. Retrieved 5 April 2017.
35. Wadman, Meredith (2022). "Prominent biologist David Sabatini out at MIT after breaching
sexual relationship policy" (https://www.science.org/content/article/prominent-biologist-david
-sabatini-out-mit-after-breaching-sexual-relationship-policy). ScienceInsider. American
Association for the Advancement of Science. Retrieved 25 April 2022.
36. Weiss, Suzy (2022). "He Was a World-Renowned Cancer Researcher.Now He's Collecting
Unemployment" (https://www.commonsense.news/p/he-was-a-world-renowned-cancer-rese
archer). Retrieved 26 August 2022.

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