End-binding protein 1 regulates the metabolic fate of CD4+ T lymphoblasts and Jurkat T cells and the organization of the mitochondrial network

Front Immunol. 2023 Jul 13:14:1197289. doi: 10.3389/fimmu.2023.1197289. eCollection 2023.

Abstract

The organization of the mitochondrial network is relevant for the metabolic fate of T cells and their ability to respond to TCR stimulation. This arrangement depends on cytoskeleton dynamics in response to TCR and CD28 activation, which allows the polarization of the mitochondria through their change in shape, and their movement along the microtubules towards the immune synapse. This work focus on the role of End-binding protein 1 (EB1), a protein that regulates tubulin polymerization and has been previously identified as a regulator of intracellular transport of CD3-enriched vesicles. EB1-interferred cells showed defective intracellular organization and metabolic strength in activated T cells, pointing to a relevant connection of the cytoskeleton and metabolism in response to TCR stimulation, which leads to increased AICD. By unifying the organization of the tubulin cytoskeleton and mitochondria during CD4+ T cell activation, this work highlights the importance of this connection for critical cell asymmetry together with metabolic functions such as glycolysis, mitochondria respiration, and cell viability.

Keywords: EB1; T cell receptor; cell asymmetry; cytoskeleton; glycolysis; mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD28 Antigens / metabolism
  • CD4-Positive T-Lymphocytes* / metabolism
  • Cytoskeleton / metabolism
  • Humans
  • Immunological Synapses
  • Jurkat Cells
  • Membrane Potential, Mitochondrial
  • Microtubule-Associated Proteins* / metabolism
  • Mitochondria* / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Tubulin / metabolism

Substances

  • MAPRE1 protein, human
  • Microtubule-Associated Proteins
  • Tubulin
  • Receptors, Antigen, T-Cell
  • CD28 Antigens

Grants and funding

This study was supported by grants S2022/BMD-7209-INTEGRAMUNE-CM to NBMC from the Madrid Regional Government, PDC2021-121719-I00 and PLEC2022-009298 (AEI/FEDER, UE) from the Spanish Ministry of Economy and Competitiveness (MINECO). Work in the MI lab is funded by grant PID2020-114148RB-I00 from the Spanish Ministry of Science and Innovation MCIN/AEI/ 10.13039/501100011033, which was in part granted with FEDER funding (EC). CIBER Cardiovascular (Fondo de Investigación Sanitaria del Instituto de Salud Carlos III and co-funding by Fondo Europeo de Desarrollo Regional FEDER). ÁG-M is supported by an Investigo Grant by SEPE (Fondos de Resiliencia), Gobierno de España. SR is supported by a Sara Borrell fellowship from ISCIII and DC-F is supported by a fellowship from “la Caixa” Foundation (LCF/BQ/DR19/11740010). CS is supported by PEJ-2021-TL/BMD-21204 “Garantía Juvenil” grant form Comunidad de Madrid. ML-P is a FPI fellowship (PRE2021-097478) from the Spanish Ministry of Science and Innovation. The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation. The CNIC is a Severo Ochoa Center of Excellence (MINECO award CEX2020-001041-S). Funding agencies have not intervened in the design of the studies, with no copyright over the study.