An actin-stabilizing peptide conjugate deduced from the major outer sheath protein of the bacterium Treponema denticola.
A synthetic peptide conjugated to bovine serum albumin, P34(BSA), based on a 10-mer in the deduced amino acid sequence of the major outer sheath protein of Treponema denticola, was found to stabilize actin filaments of fibroblasts. Pretreatment of cells with P34(BSA) inhibited the actin disruption induced by cytochalasin D and latrunculin B. P34(BSA) was taken up by the cells and localized among actin filaments. P34(BSA) bound actin from fibroblast lysates, and cell exposure to P34(BSA) led to the activation of RhoA, a key regulator of actin filament assembly in fibroblasts. Exposure of fibroblasts to P34(BSA) retarded their migration on a collagen substratum. P34(BSA) also inhibited chemotaxis of murine neutrophils. Our findings with a novel peptide conjugate imply that bacterial proteins known to perturb the cytoskeleton represent a rich source of molecular models upon which to design synthetic reagents for modulating actin-dependent cellular functions.
Amin
Mohsen
M
CIHR Group in Matrix Dynamics and Dental Research Institute, University of Toronto, Toronto, Ontario, Canada.
Grove
David A
DA
Kapus
András
A
Glogauer
Michael
M
Ellen
Richard P
RP
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002633:Chemotaxis / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000494:pharmacology; D048373:Treponema denticola / Q000737:chemistry*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D010455:Peptides; C066737:RHOA protein, human; D012710:Serum Albumin, Bovine; D020742:rhoA GTP-Binding Protein