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

Abstract

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.

• Authors: Makoto Nakashima, Mariko Watanabe, Kaoru Uchimaru, Ryouichi Horie
• Journal: Biology of the cell (Biol Cell) Vol. 110 Issue 5 Pg. 109-124 (May 2018) ISSN: 1768-322X [Electronic] England
• PMID: 29431186 (Publication Type: Journal Article)
• Copyright: © 2018 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

Chemical References

• Actins
• CD30 Ligand
• Ki-1 Antigen
• TNFSF8 protein, human
• Calcium

Topics

• Actins (metabolism)
• Animals
• Biological Transport
• CD30 Ligand (metabolism)
• CHO Cells
• Calcium (metabolism)
• Cell Membrane (metabolism)
• Cricetinae
• Cricetulus
• HeLa Cells
• Hodgkin Disease (metabolism, pathology)
• Humans
• Ki-1 Antigen (metabolism)
• Necrosis
• Signal Transduction
• Tumor Cells, Cultured