Details

Autor(en) / Beteiligte

• Nakashima, Makoto
• Watanabe, Mariko
• Uchimaru, Kaoru
• Horie, Ryouichi

Titel

Trogocytosis of ligand–receptor complex and its intracellular transport in CD30 signalling

Ist Teil von

• Biology of the cell, 2018-05, Vol.110 (5), p.109-124

Ort / Verlag

England

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Wiley Online Library

Beschreibungen/Notizen

• Background Information CD30, which is characteristically expressed in classical Hodgkin lymphoma (cHL), is thought to transduce signals by ligation of trimerised CD30 ligand (CD30L) on the surface of surrounding cells and recruitment of downstream molecules. In this report, we propose a new mechanism for CD30 signalling by its ligand. We prepared two stable transformants, CHO cells expressing CD30L fused to mCherry and HeLa cells expressing CD30 fused to GFP. Results Co‐culture of these cells triggered clustering of CD30 and CD30L at the cellular interface, formation of multiple CD30L–CD30 complexes, internalisation of these complexes with a portion of the plasma membrane into the HeLa cells, and intracellular transport to the lysosomal compartment. The internalisation process was significantly inhibited by actin polymerisation inhibitors. The CD30L–CD30 interaction was found to trigger active signalling processes, as measured by Ca2+ influx, and similar mechanisms were observed using cHL cell lines. Conclusions These results suggest that CD30 extracts CD30L from CD30L‐expressing cells by actin‐mediated trogocytosis, resulting in the generation of signalosomes, intracellular signalling, lysosomal degradation and a subsequent refractory phase. We postulate that similar processes may operate in tumours endogenously expressing CD30. These observations thus provide new insights into our understanding of the biological roles of CD30 in normal and malignant cells and, in particular, in cHL. Significance This study suggests a novel model of CD30 signalling that provides new insights into the biological roles of CD30 and other members of this family in normal and malignant cells. Research article New insights into the biological roles of CD30 in normal and malignant cells and, in particular, in classical Hodgkin lymphoma. CD30 bites off CD30L in a trogocytic manner, resulting in actin‐mediated internalisation of the complex, generation of the signalosomes, intracellular signalling, lysosomal degradation and a subsequent refractory phase.