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Primary Faculty
Carolyn Machamer, Ph.D.
Professor
Department of Cell Biology
Johns Hopkins University School of Medicine
725 N. Wolfe St., 105 WBSB
Baltimore, MD 21205
Telephone: 410-955-1809 (Office)
410-955-9650 (Lab)
Fax: 410-955-4129
Email: machamer@jhmi.edu
Website: N/A
Affiliations: Director, BCMB Graduate Program

 

 

 

 

 

 

 

 

Research Topic:  Golgi complex structure/function; apoptosis; intracellular virus assembly; coronaviruses; SARS; intracellular protein trafficking

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.  The Golgi complex has an unusual structure, particularly in vertebrates, where stacks of cisternal membranes are clustered into a ribbon structure near the nucleus.  One goal of our research is to understand the role of this structure in Golgi function.  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.  Several golgins, including golgin-160, are substrates for caspase cleavage during programmed cell death (apoptosis).  Our hypothesis is that specific stress 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 vertebrate pathogens that 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.

Selected Publications

Machamer, C.E. 2013. Accommodation of large cargo within Golgi cisternae. Histochem. Cell Biol., 140:261-269.

Ruch, T.R. and C.E. Machamer.  2011. The hydrophobic domain of the infectious bronchitis virus E protein alters the host secretory pathway and is important for release of infectious virus.  J. Virol. 85:675-685.

Zuckerman, D.M. S.W. Hicks, G. Charron, H.C. Hang, and C.E. Machamer.  2011.  Differential regulation of two palmitoylation sites in the cytoplasmic tail of the beta-1 adrendergic receptor. J. Biol. Chem. 286:19014-23.

Cohen, J.R., L.D. Lin and C.E. Machamer. 2011.  Identification of a Golgi targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein.  J. Virol. 85:5794-5803.

Chandran, S. and C.E. Machamer. 2010. Golgi organization and stress sensing.  The Golgi apparatus: Structure, Functions and Mechanisms.  (Nova Science, Inc, Hauppauge NY).

McBride, C.E. and C.E. Machamer.  2010. Palmitoylation of SARS-CoV S protein is necessary for partitioning into detergent-resistant membranes and cell-cell fusion but not interaction with M protein.  Virology 405:139-148.

McBride, C.E. and C.E. Machamer. 2009 A single tyrosine in the SARS coronavirus membrane protein is important for interaction with the spike protein. J. Virol. 84:1891-1901.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

 

 

 

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Updated: 8/20/13

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