Centrosome Polarization in T Cells: A Task for Formins

Laura Andrés-Delgado,Olga M Antón,Miguel Angel Alonso

doi:10.3389/fimmu.2013.00191

Abstract

T-cell antigen receptor (TCR) engagement triggers the rapid reorientation of the centrosome, which is associated with the secretory machinery, toward the immunological synapse (IS) for polarized protein trafficking. Recent evidence indicates that upon TCR triggering the INF2 formin, together with the formins DIA1 and FMNL1, promotes the formation of a specialized array of stable detyrosinated MTs that breaks the symmetrical organization of the T-cell microtubule (MT) cytoskeleton. The detyrosinated MT array and TCR-induced tyrosine phosphorylation should coincide for centrosome polarization. We propose that the pushing forces produced by the detyrosinated MT array, which modify the position of the centrosome, in concert with Src kinase dependent TCR signaling, which provide the reference frame with respect to which the centrosome reorients, result in the repositioning of the centrosome to the IS.

Highlights

T cells polarize at the cell-to-cell contact in response to appropriate antigens presented by an antigen-presenting cell (APC), forming a surface subdomain known as the immunological synapse (IS) [1, 2]
Despite the time that has passed since and the importance of the process of MT-organizing center (MTOC) reorientation to T-cell function, little progress has been made toward determining the nature of the tubulin modifications required for MT cytoskeleton remodeling, the mechanism by which MTs are stabilized after T-cell antigen receptor (TCR) engagement, the identification of the machinery involved, or the exact role of MTs in MTOC reorientation
We have integrated recent results concerning the role of formins in MT remodeling with previous observations, including the participation of the MT cytoskeleton and the requirement for Src kinase dependent TCR signaling in MTOC reorientation

Summary

Introduction

T cells polarize at the cell-to-cell contact in response to appropriate antigens presented by an antigen-presenting cell (APC), forming a surface subdomain known as the immunological synapse (IS) [1, 2]. We have integrated recent results concerning the role of formins in MT remodeling with previous observations, including the participation of the MT cytoskeleton and the requirement for Src kinase dependent TCR signaling in MTOC reorientation. In addition to localizing to the plasma membrane, DIA1, FMNL1, and INF2 distribute along MTs and at the MTOC in resting T cells.

Results

Conclusion