Centrosome polarization in T cells: a task for formins

Area of Science:

• Immunology
• Cell Biology
• Cytoskeleton Dynamics

Background:

• T-cell antigen receptor (TCR) engagement is crucial for T-cell activation and function.
• Centrosome reorientation towards the immunological synapse (IS) is essential for polarized protein secretion during T-cell activation.
• The T-cell microtubule (MT) cytoskeleton undergoes dynamic reorganization upon TCR triggering.

Purpose of the Study:

• To investigate the role of formins and detyrosinated microtubules in centrosome polarization following TCR engagement.
• To elucidate the interplay between microtubule dynamics and TCR signaling in directing centrosome repositioning to the IS.

Main Methods:

• Analysis of microtubule stability and detyrosination in T-cells upon TCR stimulation.
• Investigating the function of formins (INF2, DIA1, FMNL1) in T-cell cytoskeleton organization.
• Exploring the contribution of Src kinase signaling in TCR-mediated centrosome reorientation.

Main Results:

• TCR triggering induces the formation of a stable, detyrosinated microtubule array, disrupting symmetrical MT organization.
• Formins INF2, DIA1, and FMNL1 are implicated in promoting this specialized detyrosinated MT array.
• Centrosome polarization requires the coincidence of the detyrosinated MT array and TCR-induced tyrosine phosphorylation.

Conclusions:

• The detyrosinated MT array generates pushing forces that influence centrosome positioning.
• Src kinase-dependent TCR signaling provides the directional cue for centrosome reorientation.
• Combined MT-generated forces and TCR signaling orchestrate centrosome repositioning to the IS for effective T-cell function.