Chris Lockhart, PhDResearch Assistant ProfessorGeorge Mason University

Discovery of actinator, actin-derived bioactive peptides that modulate cytoskeleton and actin-related cellular activities.

Yi, F., Guo, J., Vo, T. T., Hetrick, B., Haikerwal, A., Zhou, Z., Sealey, L., He, S., Han, Y., Chilin, L., Spear, M., Yu, D., Kim, Y., Kashanchi, F., Zhou, T., Xu, X., Lockhart, C., & Wu, Y.

Publication Details

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ActinPeptidesCytoskeleton

Abstract

The cortical actin cytoskeleton serves as a structural support and force-generating machinery in cells, but the actin meshwork can also act as a barrier, hindering the delivery of extracellular substances. To address the issue of the cortical actin barrier, we engineered synthetic libraries of human β-actin–derived peptides to promote actin dynamics. Here, we report the discovery of six major peptides, collectively termed actinators, that are biologically active in selective modulation of actin-related cellular activities. Using retro- and lentiviral vector transduction of CAR T cells as a model, we demonstrate that an actinator markedly enhances viral vector transduction 20- to 30-fold. An individual actinator can also selectively modulate cellular functions such as regulating surface receptors, enhancing T cell adhesion, and promoting the cellular uptake of exosomes. Molecular docking and protein phosphorylation studies confirmed that actinators can modulate actin-binding proteins like cofilin. Actinators represent a class of actin-derived bioactive peptides with diverse applications in gene and immune therapies, drug delivery, and disease treatment.

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