Amin Mohsen, Grove David A, Kapus András, Glogauer Michael, Ellen Richard P
CIHR Group in Matrix Dynamics and Dental Research Institute, University of Toronto, Toronto, Ontario, Canada.
Cell Motil Cytoskeleton. 2007 Sep;64(9):662-74. doi: 10.1002/cm.20213.
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.
一种与牛血清白蛋白偶联的合成肽P34(BSA)，它基于齿垢密螺旋体主要外鞘蛋白推导氨基酸序列中的一个10聚体，被发现可稳定成纤维细胞的肌动蛋白丝。用P34(BSA)预处理细胞可抑制细胞松弛素D和拉春库林B诱导的肌动蛋白破坏。P34(BSA)被细胞摄取并定位在肌动蛋白丝之间。P'34(BSA)结合成纤维细胞裂解物中的肌动蛋白，细胞暴露于P34(BSA)会导致RhoA激活，RhoA是成纤维细胞中肌动蛋白丝组装的关键调节因子。将成纤维细胞暴露于P34(BSA)会阻碍它们在胶原蛋白基质上的迁移。P34(BSA)还抑制小鼠中性粒细胞的趋化性。我们对一种新型肽偶联物的研究结果表明，已知会干扰细胞骨架的细菌蛋白是丰富的分子模型来源，可据此设计用于调节肌动蛋白依赖性细胞功能的合成试剂。
