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Carolyn W. Slayman |
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Sterling Professor of Genetics; Professor of Cellular & Molecular Physiology
Deputy Dean for Academic & Scientific Affairs |
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* B.A. Swarthmore College, 1958
* Ph.D. Rockefeller University, 1963
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| Research Interests: | |
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* Genetics of Ion Transport
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| Honors: | |
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* D.Sc. (hon.), Bowdoin College
* Deborah Morton Award, Westbrook College
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| Research in Carolyn Slayman’s laboratory uses the plasma-membrane H+-ATPase of yeast
(Saccharomyces cerevisiae) as a simple model for studies on P-type cation pumps, a physiologically
important family that includes the Na+,K+-, H+,K+-, and Ca2+-ATPases of animal cells. These pumps
control the ionic composition of cells; many of them also serve as important drug targets (e.g.,
for cardiac glycosides in the case of Na+,K+-ATPase and anti-ulcer drugs in the case of gastric
H+,K+-ATPase).
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| Current Research: | |
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| Over the past several years, the Slayman laboratory has constructed a large collection of site-directed
mutants and used them to explore structure-function relationships in key regions of the 100 kDa H+-ATPase.
Results of particular significance include: (1) discovery of a 13-amino acid stretch in stalk segment 4
within which mutations disrupt the interaction between the catalytic domain of the ATPase (located in the
cytoplasm) and the proton channel (embedded in the membrane); and (2) clear implication of one face of
stalk segment 5 in the metabolic activation of the ATPase by glucose. Cysteine residues have now been
introduced into both regions, and methods are being developed to track conformational changes by means
of fluorescent sulfhydryl reagents. With a recently published high resolution structure of sarcoplasmic
reticulum Ca2+-ATPase as a template, biophysical data from the H+-ATPase mutants should yield helpful
insights into the molecular mechanism by which ATP hydrolysis is coupled to cation transport.
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In parallel, the H+-ATPase is being used as a tool to probe the way in which newly synthesized plasma
membrane proteins are delivered from the endoplasmic reticulum to the cell surface, as well as the
quality control mechanisms that remove poorly folded or otherwise defective proteins. During the
past year, a nested series of truncations has been constructed and has provided intriguing evidence
for an oligomerization step at the C-terminus of the ATPase; oligomerization appears to occur early
in the secretory pathway and to be essential for normal biogenesis.
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| Representative Publications: | |
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Morsomme, P., Slayman, C.W., and Goffeau (2000) Mutagenic study of the structure, function, and biogenesis
of the yeast plasma membrane H+-ATPase. BBA Biomembrane Reviews 1469:133-157.
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| Ferreira, T., Mason, A.B., and Slayman, C.W. (2001) The yeast Pma1 proton pump: a model for understanding
the biogenesis of plasma membrane proteins. J. Biol. Chem. 276:29613-29616.
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| Ferreira, T., Mason, A.B., Pypaert, M., Allen, K.E., and Slayman, C.W. (2002) Quality control in the yeast secretory pathway: a misfolded
Pma1 H+-ATPase reveals two checkpoints. J. Biol. Chem. 277:21027-21040.
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Lecchi, S., Allen, K. E., Pardo, J. P., Mason, A. B., and Slayman, C. W. (2005)
"Conformational changes of yeast plasma membrane H+-ATPase during activation by
glucose: role of Thr912 in the carboxy-terminal tail." Biochemistry 44:16624-16632
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| Mason, A. B., Allen, K. E., and Slayman, C. W. (2006) "Effects of C-terminal
truncations on trafficking of the yeast plasma membrane H+-ATPase."
Biological Chemistry 281:23887-23898
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