Abstract
Membrane proteins endocytosed at the cell surface as vesicular cargoes are sorted at early endosomes for delivery to lysosomes for degradation or alternatively recycled to different cellular destinations. Cargo recycling is orchestrated by multimolecular complexes that include the retromer, retriever, and the WASH complex, which promote the polymerization of new actin filaments at early endosomes. These endosomal actin pools play a key role at different steps of the recycling process, from cargo segregation to specific endosomal subdomains to the generation and mobility of tubulo-vesicular transport carriers. Local F-actin pools also participate in the complex redistribution of endomembranes and organelles that leads to the acquisition of cell polarity. Here, we will present an overview of the contribution of endosomal F-actin to T-cell polarization during assembly of the immune synapse, a specialized membrane domain that T cells form at the contact with cognate antigen-presenting cells.
Highlights
Surface expression of plasma membrane (PM)-associated receptors is dynamically regulated through constitutive or ligand-dependent endocytosis
Upon T-cell receptor (TCR) engagement, endosomal trafficking is redirected toward the contact area of the T cell with the antigen-presenting cell (APC) by local F-actin pools that act in concert with microtubules and endosomal traffic regulators (Soares et al, 2013; MartínCófreces and Sánchez-Madrid, 2018; Onnis and Baldari, 2019)
Rearrangements of TCRs, adhesion molecules, costimulatory receptors, and membrane-associated signaling mediators occurring at the region of the T-cell plasma membrane at the contact with cognate APC have been extensively investigated
Summary
Surface expression of plasma membrane (PM)-associated receptors is dynamically regulated through constitutive or ligand-dependent endocytosis. Receptor internalization, which occurs in a clathrin-dependent or clathrin-independent manner (Doherty and McMahon, 2009), results in their targeting to the endocytic pathway This pathway is orchestrated by a series of intracellular membrane-bound compartments that allow for the sorting of these molecules, referred to as cargoes, for one of two alternative fates: delivery to lysosomes or vacuoles for degradation by the endosomal sorting complex required for transport (ESCRT) and the multivesicular bodies (MVBs) compartment (Vietri et al, 2020) or targeting to the trans-Golgi network (TGN) or to the PM for reuse (Johannes and Wunder, 2011; Hsu et al, 2012). The retriever is not predicted to bind membranes; its endosomal recruitment depends on interactions with another complex, the CCC complex (McNally et al, 2017)
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