JBC Biosymposia, Inc.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M011735200 on April 18, 2001

J. Biol. Chem., Vol. 276, Issue 25, 23056-23064, June 22, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/25/23056    most recent
M011735200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wang, Q.
Right arrow Articles by Ellen, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, Q.
Right arrow Articles by Ellen, R. P.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

A Spirochete Surface Protein Uncouples Store-operated Calcium Channels in Fibroblasts
A NOVEL CYTOTOXIC MECHANISM*

Qin WangDagger , Kevin S. Ko§, András Kapus||, Christopher A. G. McCulloch§, and Richard P. EllenDagger **

From the Dagger  Dental Research Institute, the § Canadian Institutes of Health Research Group in Periodontal Physiology, Faculty of Dentistry, and the || Department of Surgery, University of Toronto and the Division of Surgery, Toronto General Hospital, Toronto, Ontario M5G 1G6, Canada

The cytotoxicity of infectious agents can be mediated by disruption of calcium signaling in target cells. Outer membrane proteins of the spirochete Treponema denticola, a periodontal pathogen, inhibit agonist-induced Ca2+ release from internal stores in gingival fibroblasts, but the mechanism is not defined. We determined here that the major surface protein (Msp) of T. denticola perturbs calcium signaling in human fibroblasts by uncoupling store-operated channels. Msp localized in complexes on the cell surface. Ratio fluorimetry showed that in cells loaded with fura-2 or fura-C18, Msp induced cytoplasmic and near-plasma membrane Ca2+ transients, respectively. Increased conductance was confirmed by fluorescence quenching of fura-2-loaded cells with Mn2+ after Msp treatment. Calcium entry was blocked with anti-Msp antibodies and inhibited by chelating external Ca2+ with EGTA. Msp pretreatment reduced the amplitude of [Ca2+]i transients upon challenge with ATP or thapsigargin. In experiments using cells loaded with mag-fura-2 to report endoplasmic reticulum Ca2+, Msp reduced Ca2+ efflux from endoplasmic reticulum stores when ATP was used as an agonist. Msp alone did not induce Ca2+ release from these stores. Msp inhibited store-operated influx of extracellular calcium following intracellular Ca2+ depletion by thapsigargin and also promoted the assembly of subcortical actin filaments. This actin assembly was blocked by chelating intracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester. The reduced amplitude of agonist-induced transients and inhibition of store-operated Ca2+ entry due to Msp were reversed by latrunculin B, an inhibitor of actin filament assembly. Thus, Msp retards Ca2+ release from endoplasmic reticulum stores, and it inhibits subsequent Ca2+ influx by uncoupling store-operated channels. Actin filament rearrangement coincident with conformational uncoupling of store-operated calcium fluxes is a novel mechanism by which surface proteins and toxins of pathogenic microorganisms may damage host cells.

* This work was supported by Canadian Institutes of Health Research (CIHR) Grant MOP-5619, a maintenance grant, and a group grant.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EMBL Data Bank with accession number(s) U66256.

Supported by a CIHR fellowship.

** To whom correspondence should be addressed. Tel.: 416-979-4917 (ext. 1-4456); Fax: 416-979-4936; E-mail: richard.ellen@utoronto.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Infect. Immun.Home page
H.-K. Jun, Y.-M. Kang, H.-R. Lee, S.-H. Lee, and B.-K. Choi
Highly Conserved Surface Proteins of Oral Spirochetes as Adhesins and Potent Inducers of Proinflammatory and Osteoclastogenic Factors
Infect. Immun., June 1, 2008; 76(6): 2428 - 2438.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
C. V. Bamford, J. C. Fenno, H. F. Jenkinson, and D. Dymock
The Chymotrypsin-Like Protease Complex of Treponema denticola ATCC 35405 Mediates Fibrinogen Adherence and Degradation
Infect. Immun., September 1, 2007; 75(9): 4364 - 4372.
[Abstract] [Full Text] [PDF]

Home page
 MicrobiologyHome page
H.-K. Jun, H.-R. Lee, S.-H. Lee, and B.-K. Choi
Mapping of the proinflammatory domains of MspTL of Treponema lecithinolyticum
Microbiology, August 1, 2007; 153(8): 2386 - 2392.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Holzhausen, L. C. Spolidorio, R. P. Ellen, M.-C. Jobin, M. Steinhoff, P. Andrade-Gordon, and N. Vergnolle
Protease-Activated Receptor-2 Activation: A Major Role in the Pathogenesis of Porphyromonas gingivalis Infection
Am. J. Pathol., April 1, 2006; 168(4): 1189 - 1199.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
B. Puthengady Thomas, C. X. Sun, E. Bajenova, R. P. Ellen, and M. Glogauer
Modulation of Human Neutrophil Functions In Vitro by Treponema denticola Major Outer Sheath Protein
Infect. Immun., March 1, 2006; 74(3): 1954 - 1957.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
A. M. Edwards, H. F. Jenkinson, M. J. Woodward, and D. Dymock
Binding Properties and Adhesion-Mediating Regions of the Major Sheath Protein of Treponema denticola ATCC 35405
Infect. Immun., May 1, 2005; 73(5): 2891 - 2898.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S.-H. Lee, K.-K. Kim, and B.-K. Choi
Upregulation of Intercellular Adhesion Molecule 1 and Proinflammatory Cytokines by the Major Surface Proteins of Treponema maltophilum and Treponema lecithinolyticum, the Phylogenetic Group IV Oral Spirochetes Associated with Periodontitis and Endodontic Infections
Infect. Immun., January 1, 2005; 73(1): 268 - 276.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. Amin, A. C. S. Ho, J. Y. Lin, A. P. Batista da Silva, M. Glogauer, and R. P. Ellen
Induction of De Novo Subcortical Actin Filament Assembly by Treponema denticola Major Outer Sheath Protein
Infect. Immun., June 1, 2004; 72(6): 3650 - 3654.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
P. D. Arora, M. Glogauer, A. Kapus, D. J. Kwiatkowski, and C. A. McCulloch
Gelsolin Mediates Collagen Phagocytosis through a Rac-dependent Step
Mol. Biol. Cell, February 1, 2004; 15(2): 588 - 599.
[Abstract] [Full Text] [PDF]

Home page
 Crit. Rev. Oral Biol. Med.Home page
M. J. Duncan
GENOMICSOF ORAL BACTERIA
Crit. Rev. Oral. Biol. Med., May 1, 2003; 14(3): 175 - 187.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.