αII-spectrin in T cells is involved in the regulation of cell-cell contact leading to immunological synapse formation?

• Published in: PloS one 2017-12, Vol.12 (12), p.e0189545-e0189545
• Main Authors: Meissner, Justyna M, Sikorski, Aleksander F, Nawara, Tomasz, Grzesiak, Jakub, Marycz, Krzysztof, Bogusławska, Dżamila M, Michalczyk, Izabela, Lecomte, Marie-Christine, Machnicka, Beata
• Format: Article
• Language: English
• Subjects: Actin; Adhesion; Antigen presentation; Antigens; Biology; Biology and Life Sciences; Biotechnology; CD45 antigen; Cell activation; Cell adhesion; Cell culture; Cytoskeleton; Defects; Dendritic cells; Depletion; Extracellular matrix; Filopodia; Gene expression; Immune response; Immunoglobulins; Immunological synapses; Immunology; Kinases; Laboratories; Lamellipodia; LFA-1 antigen; Life sciences; Lymphocytes; Lymphocytes T; Medicine and Health Sciences; Membrane proteins; Microscopy; Polymerization; Proteins; Pseudopodia; Relocation; Signal transduction; Signaling; Spectrin; Stability analysis; Synapses; T cell receptors; T-cell receptor
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0189545

T-lymphocyte activation after antigen presentation to the T-Cell Receptor (TCR) is a critical step in the development of proper immune responses to infection and inflammation. This dynamic process involves reorganization of the actin cytoskeleton and signaling molecules at the cell membrane, leading to the formation of the Immunological Synapse (IS). The mechanisms regulating the formation of the IS are not completely understood. Nonerythroid spectrin is a membrane skeletal protein involved in the regulation of many cellular processes, including cell adhesion, signaling and actin cytoskeleton remodeling. However, the role of spectrin in IS formation has not been explored. We used molecular, imaging and cellular approaches to show that nonerythroid αII-spectrin redistributes to the IS during T-cell activation. The redistribution of spectrin coincides with the relocation of CD45 and LFA-1, two components essential for IS formation and stability. We assessed the role of spectrin by shRNA-mediated depletion from Jurkat T cells and show that spectrin-depleted cells exhibit decreased adhesion and are defective in forming lamellipodia and filopodia. Importantly, IS formation is impaired in spectrin-depleted cells. Thus, spectrin may be engaged in regulation of distinct events necessary for the establishment and maturity of the IS: besides the involvement of spectrin in the control of CD45 and LFA-1 surface display, spectrin acts in the establishment of cell-cell contact and adhesion processes during the formation of the IS.