Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 301 (5640): 1734-1736

Copyright © 2003 by the American Association for the Advancement of Science

Erythrocyte G Protein-Coupled Receptor Signaling in Malarial Infection

Travis Harrison,1,2 Benjamin U. Samuel,1,2* Thomas Akompong,1,2 Heidi Hamm,3 Narla Mohandas,4 Jon W. Lomasney,1{dagger} Kasturi Haldar1,2{dagger}

Abstract: Erythrocytic mechanisms involved in malarial infection are poorly understood. We have found that signaling via the erythrocyte ß2-adrenergic receptor and heterotrimeric guanine nucleotide–binding protein (G{alpha}s) regulated the entry of the human malaria parasite Plasmodium falciparum. Agonists that stimulate cyclic adenosine 3',5'-monophosphate production led to an increase in malarial infection that could be blocked by specific receptor antagonists. Moreover, peptides designed to inhibit G{alpha}s protein function reduced parasitemia in P. falciparum cultures in vitro, and ß-antagonists reduced parasitemia of P. berghei infections in an in vivo mouse model. Thus, signaling via the erythrocyte ß2-adrenergic receptor and G{alpha}s may regulate malarial infection across parasite species.

1 Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 Chicago Avenue, Chicago, IL 60611, USA.
2 Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, 303 Chicago Avenue, Chicago, IL 60611, USA.
3 Department of Pharmacology, Vanderbilt University, Nashville, TN 37240, USA.
4 New York Blood Center, New York, NY 10021, USA.

Back to Top

* Present address: Department of Ophthalmology and Visual Sciences, University of Chicago, Room 103 Visual Science Center, Chicago, IL 60637, USA.

{dagger} To whom correspondence should be addressed. E-mail: k-haldar{at}northwestern.edu (K.H.); j-lomasney{at}northwestern.edu (J.W.L.)


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Allosteric Mechanism Induced by Protein Kinase A (PKA) Phosphorylation of Dematin (Band 4.9).
L. Chen, J. W. Brown, Y.-F. Mok, D. M. Hatters, and C. J. McKnight (2013)
J. Biol. Chem. 288, 8313-8320
   Abstract »    Full Text »    PDF »
Identification of a Novel Role for Dematin in Regulating Red Cell Membrane Function by Modulating Spectrin-Actin Interaction.
I. Koshino, N. Mohandas, and Y. Takakuwa (2012)
J. Biol. Chem. 287, 35244-35250
   Abstract »    Full Text »    PDF »
Malaria, erythrocytic infection, and anemia.
K. Haldar and N. Mohandas (2009)
Hematology 2009, 87-93
   Abstract »    Full Text »    PDF »
Red cell membrane: past, present, and future.
N. Mohandas and P. G. Gallagher (2008)
Blood 112, 3939-3948
   Abstract »    Full Text »    PDF »
Cytoplasmic remodeling of erythrocyte raft lipids during infection by the human malaria parasite Plasmodium falciparum.
S. C. Murphy, S. Fernandez-Pol, P. H. Chung, S. N. Prasanna Murthy, S. B. Milne, M. Salomao, H. A. Brown, J. W. Lomasney, N. Mohandas, and K. Haldar (2007)
Blood 110, 2132-2139
   Abstract »    Full Text »    PDF »
PfPKB, a Protein Kinase B-like Enzyme from Plasmodium falciparum: II. IDENTIFICATION OF CALCIUM/CALMODULIN AS ITS UPSTREAM ACTIVATOR AND DISSECTION OF A NOVEL SIGNALING PATHWAY.
A. Vaid and P. Sharma (2006)
J. Biol. Chem. 281, 27126-27133
   Abstract »    Full Text »    PDF »
Delivery of the Malaria Virulence Protein PfEMP1 to the Erythrocyte Surface Requires Cholesterol-Rich Domains.
S. Frankland, A. Adisa, P. Horrocks, T. F. Taraschi, T. Schneider, S. R. Elliott, S. J. Rogerson, E. Knuepfer, A. F. Cowman, C. I. Newbold, et al. (2006)
Eukaryot. Cell 5, 849-860
   Abstract »    Full Text »    PDF »
Fas-, Caspase 8-, and Caspase 3-dependent Signaling Regulates the Activity of the Aminophospholipid Translocase and Phosphatidylserine Externalization in Human Erythrocytes.
D. Mandal, A. Mazumder, P. Das, M. Kundu, and J. Basu (2005)
J. Biol. Chem. 280, 39460-39467
   Abstract »    Full Text »    PDF »
Intracellular Parasite Invasion Strategies.
L. D. Sibley (2004)
Science 304, 248-253
   Abstract »    Full Text »    PDF »
Erythrocyte detergent-resistant membrane proteins: their characterization and selective uptake during malarial infection.
S. C. Murphy, B. U. Samuel, T. Harrison, K. D. Speicher, D. W. Speicher, M. E. Reid, R. Prohaska, P. S. Low, M. J. Tanner, N. Mohandas, et al. (2004)
Blood 103, 1920-1928
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882