n
the interview below, Dr. Thomas Südhof discusses his highly
cited paper, "The synaptic vesicle cycle—a cascade of
protein-protein interactions," (Nature 375[6533]:
645-53, 22 June 1995). According to the ISI
Essential Science Indicators
Web product, this paper is currently among the five most-cited
papers in the field of Neuroscience & Behavior, with 1,339
cites to date. Dr. Südhof’s work appears in the fields of
Neuroscience & Behavior, Biology & Biochemistry, and
Molecular Biology & Genetics. Dr. Südhof is a Howard
Hughes Medical Institute investigator currently working out of
the University of Texas Southwestern Medical Center in Dallas,
where he is also the Director of the Center for Basic
Neuroscience, the Gill Distinguished Chair in Neuroscience
Research, and the Loyd B. Sands Distinguished Chair in
Neuroscience.
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Why do you think your paper is highly cited?
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“I wrote this review to synthesize the emerging data in the field, especially to communicate the concept that proteins such as SNARE, Munc18, and synaptotagmin have to work hand-in-hand in order to effect neurotransmitter release.”
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First of all, let me point out that this paper is a review, and
reviews tend to be more cited. Nevertheless, I think this is a
special review which is different from other reviews that I and
other investigators have written because it proposes a new concept:
the idea that a membrane trafficking event (synaptic vesicle
exocytosis that mediates neurotransmitter release) can be explained
as the result of a cascade or protein-protein interactions.
What are the circumstances which led you to your work?
I wrote this review to synthesize the emerging data in the field,
especially to communicate the concept that proteins such as SNARE,
Munc18, and synaptotagmin have to work hand-in-hand in order to
effect neurotransmitter release.
How would you describe the significance of this work for your
field?
I believe that, as a review, this paper provided a service: it
allowed people to connect different results, and see them as a
whole. Innumerable reviews are written in a field that are often
progress reports of a laboratory; this review—at least I think so—provided
a real assessment.
Where has this research gone since the publication of your
paper? Where do you see it going 10 years from now?
I would like to comment here primarily on my own work, because I
feel that this is work I can assess best. I think the review
stimulated our experiments that demonstrated that synaptotagmin 1 is
indeed the calcium sensor for fast neurotransmitter release. This,
in my view, is a big part of a major problem in neurobiology—how
is it possible for calcium to trigger release so quickly?—and has
led us to enter a new field, the question of the molecular basis for
the modulation of release by external signals and experience in a
synapse.
What lessons would you draw from your work to share with the
next generation of researchers?
I would rather comment on what lessons I feel are the most
important now for the practice of science. This is that we have to
remember that data are the primary currency of science, that the
claim of "function" in a study must be related to the data
directly and not be an attached claim. The major journals are now
populated by relatively simple experiments that are interpreted with
extravagant conclusions. My advice would be: look at what is
actually measured, what is observed in real terms, not at what the
authors claim this means. For example, transient transfection
studies in PC12 cells claim to delineate the fusion pore—the next
generation should be more skeptical of any conclusions that refer to
processes which are not really measured, and become concerned when
the same result is obtained with many different molecules (e.g.,
many proteins transfected into PC12 cells alter the "fusion
pore"). I believe we need a higher standard of reviewing where
papers are not graded based on how exciting the associated claims
are, but how solid the data are—this is what counts in the end.
Thomas C. Südhof, M.D.
Howard Hughes Medical Institute
Center for Basic Neuroscience
UT Southwestern Medical Center
Dallas, TX, USA
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