LRP5 and LRP6 Are Not Required for Protective Antigen–Mediated Internalization or Lethality of Anthrax Lethal Toxin

PLoS Pathogens

James H Resau¹  John J Young²  Elissa Boguslawski²  Nicholas S Duesbery²  Jennifer L Bromberg-White²  Joseph T Church²  Bart O Williams³  Cassandra Zylstra³ 

[1] Laboratory of Analytical, Cellular, and Molecular Microscopy, Van Andel Research Institute, Grand Rapids, Michigan, United States of America;Laboratory of Cancer and Developmental Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan, United States of America;Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan, United States of America

关键词: Small interfering RNAs;    Polymerase chain reaction;    Anthrax;    Toxins;    CHO cells;    Immunoblotting;    Lethality (bacteriology);    Mouse models;   

DOI  :  10.1371/journal.ppat.0030027

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Anthrax toxin (AnTx) plays a key role in the pathogenesis of anthrax. AnTx is composed of three proteins: protective antigen (PA), edema factor, and lethal factor (LF). PA is not toxic but serves to bind cells and translocate the toxic edema factor or LF moieties to the cytosol. Recently, the low-density lipoprotein receptor–related protein LRP6 has been reported to mediate internalization and lethality of AnTx. Based on its similarity to LRP6, we hypothesized that LRP5 may also play a role in cellular uptake of AnTx. We assayed PA-dependent uptake of anthrax LF or a cytotoxic LF fusion protein (FP59) in cells and mice harboring targeted deletions of Lrp5 or Lrp6. Unexpectedly, we observed that uptake was unaltered in the presence or absence of either Lrp5 or Lrp6 expression. Moreover, we observed efficient PA-mediated uptake into anthrax toxin receptor (ANTXR)–deficient Chinese hamster ovary cells (PR230) that had been stably engineered to express either human ANTXR1 or human ANTXR2 in the presence or absence of siRNA specific for LRP5 or LRP6. Our results demonstrate that neither LRP5 nor LRP6 is necessary for PA-mediated internalization or lethality of anthrax lethal toxin.

【 授权许可】

CC BY