Newly Described Peptide with Actin Stabilizing Activity
The cellular cytoskeleton functions to maintain the spatial shape and volume of mammalian cells; it is crucial for functions such as locomotion (migration), endocytosis, and phagocytosis. Actin is one of the key proteins of the cytoskeleton, and the physiologic assembly and disassembly of actin filaments in response to regulatory signals maintains homeostasis of cellular functions and responds to external stress to protect the cell. Cells move by remodeling actin filaments at their leading edge.
Inflammatory cells like neutrophils and macrophages require actin filament assembly to migrate to sites of infection or injury and to engulf microorganisms or other foreign objects. Indeed neutrophils are key cells of the innate immune protection; yet their high numbers and amplified activity have been shown to contribute significantly to inflammation-induced tissue injury.
Epithelial cells require actin filament assembly to migrate over wounds and to maintain cell-cell junctions in a protective barrier that protects the underlying connective tissue from microbes and their products and potentially toxic ingredients of ingested foods and liquids. Therefore, the cytoskeleton is a central part of the cellular machinery in virtually all cells and all tissues of the body.
Researchers at UofT have synthesized a peptide conjugate from a deduced peptide sequence within a key surface protein of a periodontal bacterium that can inhibit the migration of inflammatory cells and stabilize actin filaments of fibroblasts. The technology has been shown to:
Inhibit chemotaxis of murine neutrophils through the RhoA pathway Cause fibroblasts to produce thicker actin stress fibers
Protect fibroblasts that were pretreated with the peptide conjugate from cytoskeletal perturbation when exposed to chemical and bacterial actin-disrupting agents.
The peptide-conjugate technology:
Can be used to modulate cellular migration when investigating innate immunity or to orchestrate cellular migration in tissue engineering. That can bolster actin assembly and that protect the cytoskeleton from deleterioius effects of infectious agents or toxins may find application in treatments to promote proper wound healing. Can be used to study and modulate actin-dependent cellular function. There are a number of laboratory reagents that are highly useful in research as cytoskeletal inhibitors, but there are fewer laboratory reagents with cytoskeletal stabilizing effects. The best known actin stabilizers are extracted and prepared from biological sources. Therefore, one of the key properties of the biologically active peptide moiety of the conjugate is that it can be synthesized readily.
We are interested in licensing this technology to an experienced industrial partner, who will take the lead in developing this technology further. We are also soliciting for sponsored research collaboration agreements to further explore additional applications and improvements of this technology.
US patent application has been filed.
Amin, M. et al. An Actin-Stabilizing Peptide Conjugate Deduced From the Major Outer Sheath Protein of the Bacterium Treponema denticola. Cell Motility and the Cytoskeleton. 2007.
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