A new molecular player involved in T cell activation

Fluorescence live-cell imaging of the wild-type CLIP-170-TagRFP-T (a,b) or a phosphodeficient S312A mutant CLIP-170-TagREP-T (c) and dynein light chain (DLC)-mEGFP co-expressed in T cells. Increased dynein relocation to the center, which is responsible for MTOC repositioning, requires both stimulation and CLIP-170 phosphorylation. The boxed regions in the merged images are enlarged (right). Scale bars: 5 μm (left, 2nd left, merged) and 2 μm (right). Credit: Scientific Reports

During T-cell activation, a molecular complex known as the microtubule-organizing center (MTOC) moves to a central location on the surface of the T-cell.

Microtubules have several important functions, including determining cell shape and cell division. Thus, MTOC repositioning plays a critical role in the immune response initiated by activated T cells.

In a recent publication in Scientific Reports, the first authors Lim Wei Ming and Yuma Ito, along with their colleagues at Tokyo Institute of Technology (Tokyo Tech), provide compelling evidence that a key protein responsible for the relocation of the MTOC in activated T cells is a molecule known as CLIP-170, a microtubule-binding protein.

The researchers used live-cell imaging to uncover the mechanism of MTOC relocation. “The use of dual-color fluorescence microscopic imaging of live T cells allowed us to visualize and quantify the molecular interactions and dynamics of proteins during MTOC repositioning,” notes Dr. Sakata-Sogawa.

This technique allowed them to confirm that phosphorylation of CLIP-170 is involved in movement of the MTOC to the center of the contacted cell surface (Fig. 1); the findings were confirmed using both cells with phosphodeficient CLIP-170 mutant and cells in which AMPK, the molecule that phosphorylates and activates CLIP-170, was impaired.

Further imaging showed that CLIP-170 is essential for directing dynein, a motor protein, to the plus ends of microtubules and for anchoring dynein in the center of the cell surface (Fig. 2). Dynein then pulls on the microtubules to reposition the MTOC to its new location in the center.

“These findings shed new light on microtubule binding proteins and microtubule dynamics,” explains Dr. Tokunaga. Such research is critical, as a deeper understanding of T cell activation in the immune response, and could lead to the development of safer methods for cancer immunotherapy because presentation of CTLA-4, which is found by a 2018 Novel Prize laureate and used as a target of the therapy, is also regulated by MTOC repositioning.

Media Contact

Kazuhide Hasegawa
media@jim.titech.ac.jp
81-357-342-975

http://www.titech.ac.jp/english/index.html 

Media Contact

Kazuhide Hasegawa EurekAlert!

Alle Nachrichten aus der Kategorie: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Zurück zur Startseite

Kommentare (0)

Schreib Kommentar

Neueste Beiträge

Safe high-tech batteries for electric cars and laptops

New joint project at the University of Bayreuth Lithium-ion batteries are currently the most important category of electrical energy storage device. Their operational safety depends crucially on separators that ensure…

New study suggests supermassive black holes could form from dark matter

A new theoretical study has proposed a novel mechanism for the creation of supermassive black holes from dark matter. The international team find that rather than the conventional formation scenarios…

Tool that more efficiently analyzes ocean color data will become part of NASA program

Stevens uses machine learning-driven techniques to develop a long-awaited tool that better reveals the health of Earth’s oceans and the impacts of climate change. Researchers at Stevens Institute of Technology…

Partners & Sponsors