Cell polarity regulators, multifunctional organizers of lymphocyte activation and function

Cell polarity regulators are ubiquitous, evolutionary conserved multifunctional proteins. They contain a variety of protein–protein interaction domains endowing them the capacity to interact with cytoskeleton structures, membrane components and multiple regulatory proteins. In this way, they act in complexes and are pivotal for cell growth and differentiation, tissue formation, stability and turnover, cell migration, wound healing, and others. Hence some of these proteins are tumor suppressors. These cellular processes rely on the establishment of cell polarity characterized by the asymmetric localization of proteins, RNAs, membrane domains, or organelles that together condition cell shape and function. Whether apparently stable, as in epithelia or neurons, or very dynamic, as in immune cells, cell polarity is an active process. It involves cytoskeleton reorganization and targeted intracellular traffic, and results in cellular events such as protein synthesis, secretion and assembly taking place at defined cell poles. Multiple polarity regulators orchestrate these processes. Immune cells are particularly versatile in rapidly polarizing and assuming different shapes, so to swiftly adopt specialized behaviors and functions. Polarity regulators act in various ways in different immune cell types and at their distinct differentiation states. Here we review how cell polarity regulators control different processes and functions along T lymphocyte physiology, including cell migration through different tissues, immunological synapse formation and effector functions.