William T. Doerrler
William T. DoerrlerThe envelope of Escherichia coli and all Gram-negative bacteria is a remarkable structure consisting of two membranes, an inner membrane (IM) and an outer membrane (OM), separated by the periplasmic space. The IM is a lipid bilayer of phospholipids- mainly phosphatidylethanolamine (PE), phosphatidylglycerol (PG) and cardiolipin (CL). The OM is an asymmetric lipid bilayer consisting of an inner face of phospholipids and an outer face of lipopolysaccharide (LPS). Lipids play important roles in all cells in addition to their role as the structural components of membranes. Lipids play critical roles in protein folding and trafficking, signal transduction, and cell division, to name a few. Many exciting questions remain unanswered regarding the functions of lipids in biology.
Our genetic approaches have given us the tools to understand the functions of the highly conserved DedA family of IM proteins in membrane biology and cell division. A new temperature sensitive mutant with alterations in membrane composition and defects in cell division was isolated in a screen for novel lipid mutants. This mutant, named Lud135, has mutations in yqjA and yghB, encoding conserved and related polytopic IM proteins belonging to the DedA family. Genes that encode homologues of DedA proteins are found in most prokaryotic genomes but have not been studied to date. Genetic and biochemical approaches will allow us to gain insight into the function of this mysterious gene family.
Selected Publications:
Thompkins K, Chattopadhyay B, Xiao Y, Henk MC and Doerrler WT. Temperature Sensitivity and Cell Division Defects in an Escherichia coli yghB/yqjA Double Mutant, Encoding Related and Conserved Inner Membrane Proteins. J Bacteriology In Press, 2008.
Beck S, Marlow VL, Woodall K, Doerrler WT, James EK, and Ferguson GP. The Sinorhizobium meliloti MsbA2 protein is Essential for the Legume Symbiosis. Microbiology 154; 1258-1270, 2008.
Doerrler WT. Density Gradient Enrichment of Escherichia coli Conditional msbA Mutants. Applied and Environmental Microbiology 73; 7992-7996, 2007.
Doerrler WT. Lipid trafficking to the outer membrane of Gram-negative bacteria. Molecular Microbiology. 60; 542-552, 2006.
Doerrler WT. and Raetz CR. Loss of outer membrane proteins without inhibition of lipid export in an Escherichia coli YaeT mutant. J Biol Chem. 280; 27679-87, 2005.
Doerrler WT., Gibbons HS, Raetz CR. MsbA-dependent translocation of lipids across the inner membrane of Escherichia coli. J Biol Chem. 279; 45102-9, 2004.
Doerrler WT. and Raetz CR. ATPase activity of the MsbA lipid flippase of Escherichia coli. J Biol Chem 277; 36697-36705, 2002.
Doerrler WT., Reedy MC, Raetz CR. An Escherichia coli mutant defective in lipid export. J Biol Chem 276; 11461-11464, 2001.
Doerrler WT. and Lehrman MA. Regulation of the dolichol pathway in human fibroblasts by the endoplasmic reticulum unfolded protein response. Proc Nat Acad Sci USA 96; 13050-13055, 1999.
Doerrler WT., Ye J, Falck JR, Lehrman MA. Acylation of glucosaminyl phosphatidylinositol revisited. Palmitoyl-CoA dependent palmitoylation of the inositol residue of a synthetic dioctanoyl glucosaminyl-phosphatidylinositol by hamster membranes permits efficient mannosylation of the glucosamine residue. J Biol Chem 271; 27031-27038, 1996.
