Plectin Regulates Focal Adhesion Dynamics and Cytoskeletal Organization in Mouse Astrocytes: Implications for Reactive Astrogliosis

Abstract

Reactive astrogliosis, a hallmark of central nervous system pathologies, involves cellular responses, including morphological remodelling and upregulation of intermediate filaments such as vimentin. These changes are driven by cytoskeletal dynamics and are mediated by focal adhesions (FAs). Our study identifies plectin, a versatile cytoskeletal linker protein, as a critical modulator of FA-associated processes in mouse astrocytes. We demonstrate that plectin localizes to astrocyte FAs, where it regulates their number, maturation, turnover, and the mobility of FA components. Plectin also polarizes within FAs, depending on their maturation state, and controls the recruitment of key cytoskeletal elements particularly vimentin. In plectin-deficient astrocytes, the vimentin network exhibits impaired connectivity, accompanied by altered viscoelastic properties of the cells. In a model of reactive astrocytes FA number and size were elevated along with the expression of plectin, highlighting involvement of plectin in pathological conditions.