Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity.

Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Research Abstract Details 

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Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Abstract Text:

Karen P Fong,Cinthia M F Pacheco,Linda L Otis,Somesh Baranwal,Irene R Kieba,Gerald Harrison,Elliot V Hersh,Kathleen Boesze-Battaglia,Edward T Lally,

Actinobacillus actinomycetemcomitans produces a leukotoxin (Ltx) that kills leukocyte function-associated antigen-1 (LFA-1)-bearing cells from man, the Great Apes and Old World monkeys. The unique specificity of Ltx for the beta2 integrin, LFA-1, suggests it is capable of providing insight into the pathogenic mechanisms of Ltx and other RTX toxins. Using the Jurkat T cell line and an LFA-1-deficient Jurkat mutant (Jbeta2.7) as models, we found the initial effect of Ltx is to elevate cytosolic Ca2+ [Ca2+]c, an event that is independent of the Ltx/LFA-1 interaction. [Ca2+]c increases initiate a series of events that involve the activation of calpain, talin cleavage, mobilization to, and subsequent clustering of, LFA-1 in cholesterol and sphingolipid-rich regions of the plasma membrane known as lipid rafts. The association of Ltx and LFA-1 within lipid rafts is essential for cell lysis. Jbeta2.7 cells fail to accumulate Ltx in their raft fractions and are not killed, while cholesterol depletion experiments demonstrate the necessity of raft integrity for Ltx function. We propose that toxin-induced Ca2+ fluxes mobilize LFA-1 to lipid rafts where it associates with Ltx. These findings suggest that Ltx utilizes the raft to stimulate an integrin signalling pathway that leads to apoptosis of target cells.

Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Publishing Authors By Initials

KP Fong,CM Pacheco,LL Otis,S Baranwal,IR Kieba,G Harrison,EV Hersh,K Boesze-Battaglia,ET Lally,

For similar proteins: cytoskeletal proteins: talin research abstracts see: proteins: cytoskeletal proteins: talin research

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Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cellular microbiology

VOLUME: 8

Page Numbers: 1753-67

Journal Abbreviation: Cell. Microbiol.

ISSN: 1462-5814

DAY: 7

MONTH: 07

YEAR: 2006

Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100883691

Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Keywords Mesh Terms:

KEYWORDS: Talin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity. Information

Substance Name: Calpain

Registry Number: EC 3.4.22.-

Grant and Affiliation Information for Actinobacillus actinomycetemcomitans leukotoxin requires lipid microdomains for target cell cytotoxicity.

AFFILIATION: The Leon Levy Research Center for Oral Biology, University of Pennsylvania, Philadelphia, PA 19104-6002, USA.

Country: England

AGENCY: United States NIDCR

GRANT: DE12305

ACRONYM: DE

MEDLINETA: Cell Microbiol

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