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Infection and Immunity, January 2009, p. 52-59, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01073-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Cytoplasmic Domain of Anthrax Toxin Receptor 1 Affects Binding of the Protective Antigen{triangledown}

Mandy Y. Go, Edith M. C. Chow, and Jeremy Mogridge*

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8

Received 28 August 2008/ Returned for modification 29 September 2008/ Accepted 10 October 2008

The protective antigen (PA) component of anthrax toxin binds the I domain of the receptor ANTXR1. Integrin I domains convert between open and closed conformations that bind ligand with high and low affinities, respectively; this process is regulated by signaling from the cytoplasmic domains. To assess whether intracellular signals might influence the interaction between ANTXR1 and PA, we compared two splice variants of ANTXR1 that differ only in their cytoplasmic domains. We found that cells expressing ANTXR1 splice variant 1 (ANTXR1-sv1) bound markedly less PA than did cells expressing a similar level of the shorter splice variant ANTXR1-sv2. ANTXR1-sv1 but not ANTXR1-sv2 associated with the actin cytoskeleton, although disruption of the cytoskeleton did not affect binding of ANTXR-sv1 to PA. Introduction of a cytoplasmic domain missense mutation found in the related receptor ANTXR2 in a patient with juvenile hyaline fibromatosis impaired actin association and increased binding of PA to ANTXR1-sv1. These results suggest that ANTXR1 has two affinity states that may be modulated by cytoplasmic signals.

* Corresponding author. Mailing address: Department of Laboratory Medicine and Pathobiology, Medical Sciences Building, Rm. 6308, 1 King's College Circle, University of Toronto, Toronto, ON, Canada M5S 1A8. Phone: (416) 946-8095. Fax: (416) 978-5959. E-mail: jeremy.mogridge{at}utoronto.ca

{triangledown} Published ahead of print on 20 October 2008.

Editor: S. R. Blanke

Infection and Immunity, January 2009, p. 52-59, Vol. 77, No. 1
0019-9567/09/$08.00+0     doi:10.1128/IAI.01073-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Liao, K.-C., Mogridge, J. (2009). Expression of Nlrp1b Inflammasome Components in Human Fibroblasts Confers Susceptibility to Anthrax Lethal Toxin. Infect. Immun. 77: 4455-4462 [Abstract] [Full Text]  


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