Tubulin polymerization modulates interleukin-2 receptor signal transduction in human T cells
Jens Goebel1, Kathy Forrest, Marsha Wills-Karp
1Department of Pediatrics, University of Kentucky, Lexington, Kentucky, USA. Jens.Goebel@cchmc
Insights
Cytoskeletal changes, particularly tubulin polymerization, impact interleukin-2 receptor (IL-2R) signaling strength and receptor-cytoskeleton interactions in human T cells, influencing immune responses.
Area of Science:
- Immunology
- Cell Biology
- Cytoskeletal Dynamics
Background:
- Limited data exist on how the actin and tubulin cytoskeleton modulate cytokine receptor signaling.
- Interleukin-2 receptor (IL-2R) signaling is crucial for T cell function.
Purpose of the Study:
- To investigate the modulation of IL-2R signaling by cytoskeletal alterations.
- To examine the relationship between tubulin and actin cytoskeleton dynamics and IL-2R signaling pathways.
Main Methods:
- Studied IL-2R signaling in human T cells pretreated with phytohemagglutinin (PHA).
- Induced cytoskeletal changes using cytochalasin D, jasplaklinolide, taxol, and colchicine.
- Confirmed findings in TCR-transgenic mouse T cells stimulated with antigen.
Main Results:
- Altered tubulin polymerization significantly changed the strength of IL-2-triggered signals.
- Taxol-induced tubulin hyperpolymerization increased IL-2R beta-chain surface expression and its association with tubulin.
- The IL-2R beta-chain showed constitutive association with tubulin and weaker association with actin.
Conclusions:
- Cytoskeletal component polymerization, especially tubulin, modulates IL-2 signaling at the receptor level.
- These findings highlight a direct link between cytoskeletal organization and immune receptor signaling in T cells.
Abstract:
Few data exist on the modulation of cytokine receptor signaling by the actin or tubulin cytoskeleton. Therefore, we studied interleukin-2 receptor (IL-2R) signaling in phytohemagglutinine (PHA)-pretreated human T cells in the context of alterations in the cytoskeletal system induced by cytochalasin D (CyD), jasplaklinolide (Jas), taxol (Tax), or colchicine (Col). We found that changes in cytoskeletal tubulin polymerization altered the strength of several IL-2-triggered signals. Moreover, Tax-induced tubulin hyperpolymerization augmented the surface expression of the IL-2R ss -chain and enhanced the association of the IL-2R beta -chain with cytoskeletal tubulin. The IL-2R beta-chain, in turn, was constitutively associated with tubulin and, more weakly, actin. To exclude the possibility that these associations are artifacts caused by PHA, we confirmed them in T cells from TCR-transgenic DO 11.10 mice stimulated with their nominal antigen. We conclude that altered polymerization of cytoskeletal components, especially tubulin, is accompanied by modulation of IL-2 signaling at the receptor level.
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