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Charged MVB protein 5 is involved in T-cell receptor signaling

S. M. Wi,Yoon Min,Ki-Young Lee

Published 2016 in Experimental and Molecular Medicine

ABSTRACT

Charged multivesicular body protein 5 (CHMP5) has a key role in multivesicular body biogenesis and a critical role in the downregulation of signaling pathways through receptor degradation. However, the role of CHMP5 in T-cell receptor (TCR)–mediated signaling has not been previously investigated. In this study, we utilized a short hairpin RNA-based RNA interference approach to investigate the functional role of CHMP5. Upon TCR stimulation, CHMP5-knockdown (CHMP5KD) Jurkat T cells exhibited activation of TCR downstream signaling molecules, such as PKCθ and IKKαβ, and resulted in the activation of nuclear factor-κB and the marked upregulation of TCR-induced gene expression. Moreover, we found that activator protein-1 and nuclear factor of activated T-cells transcriptional factors were markedly activated in CHMP5KD Jurkat cells in response to TCR stimulation, which led to a significant increase in interleukin-2 secretion. Biochemical studies revealed that CHMP5 endogenously forms high-molecular-weight complexes, including TCR molecules, and specifically interacts with TCRβ. Interestingly, flow cytometry analysis also revealed that CHMP5KD Jurkat T cells exhibit upregulation of TCR expression on the cell surface compared with control Jurkat T cells. Taken together, these findings demonstrated that CHMP5 might be involved in the homeostatic regulation of TCR on the cell surface, presumably through TCR recycling or degradation. Thus CHMP5 is implicated in TCR-mediated signaling. A protein involved in processing materials moving inwards from cell membranes plays a role in regulating key cells of the immune system. The CHMP5 protein has several functions in cell signaling and materials handling. These functions include assisting the conversion of vesicles that bud inwards from the cell membrane into the organelles called endosomes and lysosomes. These organelles process, degrade and recycle cellular components and molecules taken up by cells. Ki-Young Lee and co-workers at Sungkyunkwan University in South Korea investigated the specific effect of CHMP5 in T-cells, cells of the immune system that detect and fight disease. Their work suggests that CHMP5 regulates T-cells by recycling or degrading the cell surface receptor proteins that recognize foreign invaders and diseased cells. This finding may also clarify the role of the CHMP5 protein in other cells.

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