FcRn mediates fast recycling of endocytosed albumin and IgG from early macropinosomes in primary macrophages.

Autor:	Toh WH; The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia., Louber J; The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia., Mahmoud IS; The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.; Department of Medical Laboratory Sciences, The Hashemite University, Zarqa, 13133 Jordan., Chia J; CSL Limited, Research, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria 3010, Australia., Bass GT; CSL Limited, Research, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria 3010, Australia., Dower SK; CSL Limited, Research, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria 3010, Australia., Verhagen AM; CSL Limited, Research, Bio21 Molecular Science and Biotechnology Institute, Melbourne, Victoria 3010, Australia., Gleeson PA; The Department of Biochemistry and Molecular Biology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia pgleeson@unimelb.edu.au.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2019 Oct 01; Vol. 133 (5). Date of Electronic Publication: 2019 Oct 01.
DOI:	10.1242/jcs.235416
Abstrakt:	The neonatal Fc receptor (FcRn) rescues albumin and IgG from degradation following endocytosis and thereby extends the half-life of these plasma proteins. However, the pathways for the uptake of these soluble FcRn ligands, and the recycling itinerary of the FcRn-ligand complexes, have not been identified in primary cells. Here, we have defined the recycling of human albumin and IgG in primary mouse macrophages selectively expressing the human FcRn. Albumin is internalised by macropinocytosis; in the absence of FcRn, internalised albumin is rapidly degraded, while in the presence of FcRn albumin colocalises to SNX5-positive membrane domains and is partitioned into tubules emanating from early macropinosomes for delivery in transport carriers to the plasma membrane. Soluble monomeric IgG was also internalised by macropinocytosis and rapidly recycled by the same pathway. In contrast, the fate of IgG bound to surface Fcγ receptors differed from monomeric IgG endocytosed by macropinocytosis. Overall, our findings identify a rapid recycling pathway for FcRn ligands from early macropinosomes to the cell surface of primary cells. Competing Interests: Competing interestsJ.C., S.K.D., G.T.B. and A.M.V. are employees of CSL Limited and are able to partake in employee share option schemes. Research funding from CSL Limited is provided through an Australian Research Council linkage grant collaboration. (© 2019. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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