Folding for the Immune Synapse: CCT Chaperonin and the Cytoskeleton.

Noa Beatriz Martín-Cófreces,Francisco Sánchez-Madrid,José María Valpuesta

doi:10.3389/fcell.2021.658460

Abstract

Lymphocytes rearrange their shape, membrane receptors and organelles during cognate contacts with antigen-presenting cells (APCs). Activation of T cells by APCs through pMHC-TCR/CD3 interaction (peptide-major histocompatibility complex-T cell receptor/CD3 complexes) involves different steps that lead to the reorganization of the cytoskeleton and organelles and, eventually, activation of nuclear factors allowing transcription and ultimately, replication and cell division. Both the positioning of the lymphocyte centrosome in close proximity to the APC and the nucleation of a dense microtubule network beneath the plasma membrane from the centrosome support the T cell’s intracellular polarity. Signaling from the TCR is facilitated by this traffic, which constitutes an important pathway for regulation of T cell activation. The coordinated enrichment upon T cell stimulation of the chaperonin CCT (chaperonin-containing tailless complex polypeptide 1; also termed TRiC) and tubulins at the centrosome area support polarized tubulin polymerization and T cell activation. The proteasome is also enriched in the centrosome of activated T cells, providing a mechanism to balance local protein synthesis and degradation. CCT assists the folding of proteins coming from de novo synthesis, therefore favoring mRNA translation. The functional role of this chaperonin in regulating cytoskeletal composition and dynamics at the immune synapse is discussed.

Highlights

Synaptic contacts involve cell-cell communication structures determined by the polarization of organelles and specific cell components allowing the interchange of information, such as neurotransmitters, cytokines and genetic information, based on cytoskeleton rails (Martin-Cofreces et al, 2014)
The immune synapse (IS) is a transient, dynamic cell-to-cell communication structure that forms at the interface of T cells and antigen-presenting cells (APCs)
An unresolved question is how the actin and tubulin cytoskeletons coordinate to rearrange both spatially and temporally. These two cytoskeletons are inter-connected through proteins that are able to physically link them, as well as by signaling proteins that control their dynamics, such as members of the protein kinase C (PKC) family, phospholipase C and formins such as INF2 (Quann et al, 2011; Andres-Delgado et al, 2012; Kumari et al, 2015; Murugesan et al, 2016)

Summary

Introduction

Synaptic contacts involve cell-cell communication structures determined by the polarization of organelles and specific cell components allowing the interchange of information, such as neurotransmitters, cytokines and genetic information, based on cytoskeleton rails (Martin-Cofreces et al, 2014). In T cells, the highly selective proteasome inhibitor bortezomib increased tubulin dynamics at the centrosome area near the IS (Martin-Cofreces et al, 2020), while its effect on the actin cytoskeleton is not yet reported.

Results

Conclusion