Age-associated changes in Non-muscle Myosin IIA and CXCR4 regulates increased migration induced by SDF1 in CD4+ T lymphocytes from elderly human donors. (102.8)

Abstract

Abstract Non-muscle Myosin-IIA has varied functions in T cell contractility, migration and cytokinesis. Evaluation of non-muscle Myosin-IIA in CD4+ T cells from the elderly, demonstrated not only altered association of the Myosin heavy chain with the chaperone HSP90, but also increased basal levels of protein expression, and constitutive phosphorylation of the myosin light chains. These alterations manifested as increased actomyosin complex formation in cells from the elderly, as opposed to those from young donors. Additionally, chemotactic migration in response to agonist SDF1, demonstrated increased migration index in CD4+ T cells from the elderly, when compared to those from young donors. As SDF1-mediated migration is clearly dependent on the expression of CXCR4 on T cell surface, we assessed CXCR4 levels in CD4+ T cells from young and elderly human donors. Our results for the first time demonstrate a significant increase in CXCR4 levels on the surface of T cells from the elderly, when compared to those from young donors. As Myosin-IIA regulates both the motility and endocytosis of CXCR4, we hypothesize that alterations in Myosin-IIA may underlie endocytosis of CXCR4 by SDF1 in the elderly. Thus, combined alteration in Myosin-IIA and CXCR4 levels in T lymphocytes may underlie increased motility observed during aging and may impact the strength and duration of interaction with antigen-presenting cells.