title: Direct interaction between anthrax toxin receptor 1 and the actin cytoskeleton.
abstract: The protective antigen component of anthrax toxin binds the I domain of the anthrax toxin receptors, ANTXR1 and ANTXR2, in a manner akin to how integrins bind their ligands. The I domains of integrins and ANTXR1 both have high- and low-affinity conformations, and the cytosolic tails of these receptors associate with the actin cytoskeleton. The association of ANTXR1 with the cytoskeleton correlates with weakened binding to PA, although a mechanistic explanation for this observation is lacking. Here, we identified a segment in the cytoplasmic tail of ANTXR1 required for its association with the cytoskeleton. We synthesized a 60-mer peptide based on this segment and demonstrated a direct interaction between the peptide and beta-actin, indicating that in contrast to integrins, ANTXR1 does not use an adaptor to bind the cytoskeleton. This peptide orders actin filaments into arrays, demonstrating an actin bundling activity that is novel for a membrane protein.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Kristopher M
authors.initials: KM
authors.lastname: Garlick
authors.forename: Jeremy
authors.initials: J
authors.lastname: Mogridge
mesh_terms: D000199:Actins / Q000378:metabolism*; D001483:Base Sequence; D003599:Cytoskeleton / Q000378:metabolism*; D017931:DNA Primers; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D009363:Neoplasm Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: C473287:ANTXR1 protein, human; D000199:Actins; D017931:DNA Primers; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface