We are interested in the structure and function of the Golgi complex, a ubiquitous eukaryotic organelle that plays a central role in post-translational processing and sorting of newly synthesized proteins and lipids in the secretory pathway. Towards this goal, we are studying the targeting and function of resident Golgi proteins. We are interested in the contribution of the lipid bilayer to targeting of transmembrane Golgi proteins, and in the function of a group of peripheral Golgi membrane proteins called golgins. The golgins are thought to play an important role in Golgi structure and in vesicle trafficking. We recently found that golgin-160 is a substrate for caspase cleavage during programmed cell death (apoptosis). We believe that specific apoptotic signals are transduced at Golgi membranes, and that cleavage of golgin-160 may be critical for downstream signaling events. In non-apoptotic cells, golgin-160 is involved in trafficking of specific cargo molecules, including the beta-1-adrenergic receptor, and the insulin-regulated glucose transporter, GLUT4.

The other research interest in the lab is the assembly mechanism of coronaviruses, enveloped viruses that bud into Golgi compartments. Coronaviruses are ubiquitous in vertebrates and usually cause mild respiratory or gastrointestinal disease. However, the recent emergence of severe acute respiratory syndrome (SARS), which is caused by a novel coronavirus, has sparked much interest in this group of viruses. We are addressing how coronaviruses target their envelope proteins to Golgi membranes, and how they interact with each other at the virus assembly site. We are also exploring how coronaviruses are exocytosed after they bud into the Golgi lumen. Our long-term goal is to understand the advantages of intracellular assembly for coronaviruses. A better understanding of intracellular assembly and the mechanism of exocytosis should lead to novel strategies for antiviral therapeutics.

Publications:

Chandran, S. and C.E. Machamer. 2008. Acute perturbations in Golgi organization impact de novo sphingomyelin synthesis. Traffic 9:1894-1904. Pub Med Reference

Hogue, B.G., and C.E. Machamer. 2008. Coronavirus structural proteins and virus assembly. Nidoviruses. Edited by S. Perlman, T. Gallagher, and E. Snijder. (ASM), pp. 179-200.

Sbodio, J.I. and C.E. Machamer. 2007. Identification of a redox sensitive cysteine residue in GCP60 that regulates its interaction with golgin-160. J. Biol. Chem 282:29874-29881. Pub Med Reference

McBride, C.E., J. Li, and C.E. Machamer. 2007. The cytoplasmic tail of the spike protein of the severe acute respiratory syndrome coronavirus contains a novel endoplasmic reticulum retrieval signal that binds COPI and promotes interaction with membrane protein. J. Virol., 81:2418-2428.
PubMed Reference

Hicks, S.W., T.A. Horn, J.M. McCaffery, D.M. Zuckerman,and C.E. Machamer. 2006. Golgin-160 promotes cell surface expression of the beta-1-adrenergic receptor. Traffic 7:1666-1677.
PubMed Reference

Williams, D., S.W. Hicks, C.E. Machamer, and J.E. Pessin. 2006. Golgin-160 is required for the Golgi membrane sorting of the insulin-responsive glucose transporter GLUT4 in adipocytes., Molec. Biol. Cell 17:5346-5355.
PubMed Reference

Sbodio, J.I., S.W. Hicks, D. Simon, and C.E. Machamer. 2006. GCP60 preferentially interacts with a caspase-generated golgin-160 fragment. J. Biol. Chem. 281:27924-27931.
PubMed Reference

Machamer, C.E. and S. Youn. 2006. The transmembrane domain of the infectious bronchitis virus E protein is required for efficient virus release. Adv. Exp.Med. Biol, 581:193-198.
PubMed Reference

Youn, S., E.W. Collisson, and C.E. Machamer. 2006. Transcriptional regulation of infectious bronchitis virus RNA3. Adv. Exp.Med. Biol, 581:109-12.
PubMed Reference

Pendleton, A. R. and C.E. Machamer. 2006. Differential localization and turnover of infectious bronchitis virus 3b protein in mammalian versus avian cells. Virol, 345:337-345.
PubMed Reference

Youn, S., E.W. Collisson, and C.E. Machamer. 2005. Contribution of trafficking signals in the cytoplasmic tail of the infectious bronchitis virus spike protein to virus infection. J. Virol. 79 13209-13217.
PubMed Reference

Pendleton, A.R., and C. E. Machamer. 2005. Infectious bronchitis virus 3a protein localizes to a unique punctate domain of the smooth endoplasmic reticulum. J. Virol.,79:6142-6151.
PubMed Reference

Hicks, S.W. and C.E. Machamer. 2005. Golgi structure in stress sensing and apoptosis. Biochim. Biophys. Acta 1744:406-414.
PubMed Reference

Maag, R., M. Mancini,R, A. Rosen and C. E. Machamer. 2005. Caspase-resistant golgin-160 disrupts apoptosis induced by secretory pathway stress and ligation of death receptors. Molec. Biol. Cell 16:3019-2027.
PubMed Reference

Hicks, S.W. and C.E. Machamer. 2005. Isoform-specific interaction of golgin-160 with the Golgi-associated protein PIST. J. Biol. Chem 280:28944-28951.
PubMed Reference