Articles 
d'Enfert, C, Barlowe, C, Nishikawa, S.-I., Nakano, 
A., and Schekman, R. 1991 . Structural and func- 
tional dissection of a membrane glycoprotein re- 
quired for vesicle budding from the endoplasmic 
reticulum. Mol Cell Biol 11:5727-5734. 
Feldheim, D., Rothblatt, J., and Schekman, R. 
1992. Topolog}' and functional domains of 
Sec63p, an endoplasmic reticulum membrane 
protein required for secretory protein transloca- 
tion. Mol Cell Biol 12:3288-3296. 
Griff, I.e., Schekman, R., Rothman, J.E., and 
Kaiser. C.A. 1992. The yeast SEC 17 gene product 
is functionally equivalent to mammalian a-SNAP 
protein./ 5/0/ Chem 267:12106-12115. 
Hicke. L., Yoshihisa, T., and Schekman, R. 1992. 
Sec23p and a novel 105 kD protein function as a 
multimeric complex to promote vesicle budding 
and protein transport from the endoplasmic retic- 
ulum. Mol Biol Cell 3:667-676. 
Orci, L., Ravazzola, M., Meda, P., Holcomb, C, 
Moore, H.-P., Hicke, L., and Schekman, R. 1991. 
Mammalian Sec23p homologue is restricted to 
the endoplasmic reticulum transitional cyto- 
plasm. Proc Natl Acad Set USA 88:8611-8615. 
Pryer, N.K., Wuestehube, L.J., and Schekman, R. 
1992. Vesicle-mediated protein sorting. Annu 
Rev Biochem 61:471-516. 
Romisch, K., and Schekman, R. 1992. Distinct pro- 
cesses mediate glycoprotein and glycopeptide ex- 
port from the endoplasmic reticulum in Sacchar- 
omyces cerevisiae. Proc Natl Acad Set USA 
89:7227-7231. 
Sanders, S.L., and Schekman, R. 1992. Polypeptide 
translocation across the endoplasmic reticulum 
membrane./ 5/0/ Chem 267:13791-13794. 
Sanders, S.L., Whitfield, KM., Vogel, J.P., Rose, 
M.D., and Schekman, R.W. 1992. Sec6lp and 
BiP directly facilitate polypeptide translocation 
into the ER. Cell 69:353-365. 
Schekman, R. 1992. Genetic and biochemical anal- 
ysis of vesicular traffic in yeast. Curr Opin Cell 
Biol 4:587-592. 
Stirling, C.J., Rothblatt, J., Hosobuchi, M., Deshaies, 
R., and Schekman, R. 1992. Protein transloca- 
tion mutants defective in the insertion of integral 
membrane proteins into the endoplasmic reticu- 
lum. Mol Biol Cell 3:129-142. 
STUDIES IN BACTERIAL PATHOGENESIS 
Gary K. Schoolnik, M.D., Associate Investigator 
Many bacterial species that are pathogenic for hu- 
mans exist in a variety of environmental habitats that 
differ greatly with respect to temperature, the avail- 
ability of nutrients, and the concentrations of sim- 
ple chemical compounds including oxygen, iron, 
calcium, and phosphate. It now seems likely, based 
on studies from several laboratories, that physico- 
chemical parameters of this kind serve as markers of 
a particular habitat, leading to the induction of bac- 
terial genes that form an adaptive response. 
Particularly useful examples of this phenomenon 
are the enteric gram-negative bacteria, especially 
pathogenic Escherichia coli, the Saltnonellae, and 
Vibrio cholerae (the agent of Asiatic cholera) . The 
principal biomass of each of these may not be in the 
intestines of animals and humans but rather in sew- 
age, water, and soil, where they can exist as free- 
living entities or in association with plants and other 
simple organisms. The genetic basis for their capac- 
ity to survive in these extraintestinal niches has not 
been much studied by medical microbiologists but 
was probably acquired early in their evolution — 
prior to the arrival of vertebrates — and arguably un- 
derlies their capacity to persist as successful biologi- 
cal entities in nature. 
On their transfer from one of these habitats to the 
human intestine through the ingestion of contami- 
nated food or water, a rapid and dramatic change in 
bacterial metabolism and gene expression occurs, 
and new proteins are elaborated that allow the or- 
ganism to attach to mucous membranes, secrete po- 
tent enterotoxins, or enter epithelial cells. What 
role the intestinal phase of their life cycles might 
play in the ecology of these organisms and the origin 
of the genes that subserve this phase are largely un- 
answered questions. Possibly, as a result of signifi- 
cantly increased replication rates in the intestine, 
the organisms are shed in large numbers in the feces, 
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