What Is the Role of Giant Endosomal Sorting Complexes Required for Transport (ESCRT) Structures in T Cell Activation?

TL;DR

This paper investigates the role of large ESCRT structures in T cell activation and finds they are involved in membrane repair, not immune synapse formation.

Contribution

The study challenges the assumed role of giant ESCRT structures in immunological synapses, revealing their exclusive involvement in plasma membrane stability.

Findings

Giant ESCRT structures form in specific culturing conditions and lack F-actin.

Structures are found at membrane damage sites, suggesting a role in membrane repair.

No evidence supports their presence at immunological synapses between DCs and T cells.

Abstract

Our lab recently discovered uniquely large (multiple micrometres) ring‐shaped cellular structures composed of endosomal sorting complexes required for transport (ESCRT) proteins. These structures are formed by tissue infiltrating fibroblasts, dendritic cells (DCs) and macrophages but only in specific culturing conditions, notably in dense three‐dimensional collagen matrices or without serum on glass supports. We also found that the structures are devoid of F‐actin and form at membrane damage sites, suggesting a role of these structures in membrane repair. Another possibility is that these structures have a role in the immunological synapses (IS) with T cells, because they surround clusters of tetraspanins and integrins that have known roles at the IS. Therefore, we tested the hypothesis that giant ESCRT structures are present at the IS between DCs and T cells and contribute to its stability or signaling. Although we occasionally observed enrichment of ESCRT proteins at the interface between DCs, we do not observe this at the IS between human monocyte‐derived DCs (moDCs) and allogenic T cells. Thus, our data do not support a role for the giant worm‐shaped ESCRT structures at the IS, and suggest that they solely are involved in plasma membrane stability and integrity.

The article explores the discovery of unusually large, ring‐shaped ESCRT protein structures formed by immune and stromal cells. It investigates their formation, composition, and potential roles in immune synapse formation. The findings challenge assumptions about their function in immunological synapses, suggesting an exclusive role in maintaining plasma membrane integrity.

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