{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T20:47:39Z","timestamp":1781383659075,"version":"3.54.1"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>Background Information<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Co\u2010culture of these cells triggered clustering of CD30 and CD30L at the cellular interface, formation of multiple CD30L\u2013CD30 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\u2013CD30 interaction was found to trigger active signalling processes, as measured by Ca<jats:sup>2+<\/jats:sup> influx, and similar mechanisms were observed using cHL cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that CD30 extracts CD30L from CD30L\u2010expressing cells by actin\u2010mediated 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1111\/boc.201800002","type":"journal-article","created":{"date-parts":[[2018,2,12]],"date-time":"2018-02-12T10:22:38Z","timestamp":1518430958000},"page":"109-124","source":"Crossref","is-referenced-by-count":24,"title":["Trogocytosis of ligand\u2013receptor complex and its intracellular transport in CD30 signalling"],"prefix":"10.1111","volume":"110","author":[{"given":"Makoto","family":"Nakashima","sequence":"first","affiliation":[{"name":"Department of Molecular Hematology Faculty of Molecular Medical Biology Graduate School of Medical Sciences Kitasato University  Minami\u2010ku Sagamihara Kanagawa 252\u20100374 Japan"},{"name":"Laboratory of Tumor Cell Biology Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences University of Tokyo  Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology Faculty of Molecular Medical Biology Graduate School of Medical Sciences Kitasato University  Minami\u2010ku Sagamihara Kanagawa 252\u20100374 Japan"},{"name":"Division of Hematology Department of Laboratory Sciences School of Allied Health Sciences Kitasato University  Minami\u2010ku Sagamihara Kanagawa 252\u20100373 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Uchimaru","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Cell Biology Department of Computational Biology and Medical Sciences Graduate School of Frontier Sciences University of Tokyo  Minato\u2010ku Tokyo 108\u20108639 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-2290","authenticated-orcid":false,"given":"Ryouichi","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematology Faculty of Molecular Medical Biology Graduate School of Medical Sciences Kitasato University  Minami\u2010ku Sagamihara Kanagawa 252\u20100374 Japan"},{"name":"Division of Hematology Department of Laboratory Sciences School of Allied Health Sciences Kitasato University  Minami\u2010ku Sagamihara Kanagawa 252\u20100373 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1184"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3834"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(97)00108-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.1998.18.915"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.08.004"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90180-K"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.4049\/jimmunol.151.5.2380","article-title":"CD30 is a signal\u2010transducing molecule that defines a subset of human activated CD45RO+ T cells","volume":"151","author":"Ellis T.M.","year":"1993","journal-title":"J. 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