Role of Drebrin at the Immunological Synapse

Although drebrin was first described in neurons, it is also expressed in cells of the immune system, such as T lymphocytes and mast cells. Another member of the drebrin family of proteins, mammalian actin-binding protein 1 (mAbp-1) is more widely expressed and plays important roles in the function of macrophages, polymorphonuclear neutrophils, and B lymphocytes. We will briefly discuss on the function of mAbp-1 and drebrin in immune cells with emphasis on T cells. Specifically, drebrin enables the immune responses of CD4⁺ T lymphocytes. T cells are activated after the recognition of an antigen presented by antigen-presenting cells through cognate cell-cell contacts called immunological synapses (IS). In CD4⁺ T cells, drebrin associates with the chemokine receptor CXCR4, and both molecules redistribute to the IS displaying similar dynamics. Through its interaction with CXCR4 and the actin cytoskeleton, drebrin regulates T cell activation. CD4⁺ T cells are one of the main targets for the human immunodeficiency virus (HIV)-1. This virus utilizes the IS structure to be transmitted to uninfected cells, forming cell-cell contacts called virological synapses (VS). Interestingly, drebrin negatively regulates HIV-1 infection of CD4⁺ T lymphocytes, by regulating actin polymerization at the VS.