Rab17 Mediates Intermixing of Phagocytosed Apoptotic Cells with Recycling Endosomes

Overview

Journal Small GTPases

Specialties Biochemistry
Cell Biology

Date 2017 May 5

PMID 28471261

Citations 14

Authors

Charles Yin

Dean Argintaru

Bryan Heit

Affiliations

Soon will be listed here.

Abstract

Efferocytosis-the phagocytic removal of apoptotic cells-is required for preventing the presentation of apoptotic cell-derived antigens. This process is regulated by Rab17-dependent sorting of efferocytosed cargos from the phagolysosome to recycling endosomes. In this study we demonstrate that Rab17 is rapidly recruited to efferosomes, followed by migration of the efferosome to the cell center where it intermixes with lysosomes and undergoes Rab17-dependent vesiculation. These efferosome-derived vesicles then traffic in a Rab17-dependent manner to the cell periphery, where they transfer cargo to recycling endosomes. Combined, our observations support a model wherein efferosomes migrate to the cell center to acquire degradative enzymes, followed by peripheral migration to prevent further phagolysosome maturation and to enable cargo transfer to recycling endosomes.

Citing Articles

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References

Elliott M, Ravichandran K . The Dynamics of Apoptotic Cell Clearance. Dev Cell. 2016; 38(2):147-60. PMC: 4966906. DOI: 10.1016/j.devcel.2016.06.029. View

Rupper A, Grove B, Cardelli J . Rab7 regulates phagosome maturation in Dictyostelium. J Cell Sci. 2001; 114(Pt 13):2449-60. DOI: 10.1242/jcs.114.13.2449. View

Rocha N, Neefjes J . MHC class II molecules on the move for successful antigen presentation. EMBO J. 2007; 27(1):1-5. PMC: 2206127. DOI: 10.1038/sj.emboj.7601945. View

Canton J, Khezri R, Glogauer M, Grinstein S . Contrasting phagosome pH regulation and maturation in human M1 and M2 macrophages. Mol Biol Cell. 2014; 25(21):3330-41. PMC: 4214780. DOI: 10.1091/mbc.E14-05-0967. View

Johnson D, Ostrowski P, Jaumouille V, Grinstein S . The position of lysosomes within the cell determines their luminal pH. J Cell Biol. 2016; 212(6):677-92. PMC: 4792074. DOI: 10.1083/jcb.201507112. View

Hansen G, Niels-Christiansen L, Immerdal L, Hunziker W, Kenny A, Danielsen E . Transcytosis of immunoglobulin A in the mouse enterocyte occurs through glycolipid raft- and rab17-containing compartments. Gastroenterology. 1999; 116(3):610-22. DOI: 10.1016/s0016-5085(99)70183-6. View

Fonseca J, Edwards J, Blades S, Goulding N . Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich microenvironments. Arthritis Rheum. 2002; 46(5):1210-6. DOI: 10.1002/art.10207. View

Roberts R, Barbieri M, Ullrich J, Stahl P . Dynamics of rab5 activation in endocytosis and phagocytosis. J Leukoc Biol. 2000; 68(5):627-32. View

Kinchen J, Doukoumetzidis K, Almendinger J, Stergiou L, Tosello-Trampont A, Sifri C . A pathway for phagosome maturation during engulfment of apoptotic cells. Nat Cell Biol. 2008; 10(5):556-66. PMC: 2851549. DOI: 10.1038/ncb1718. View

10.

Cho K, Walseng E, Ishido S, Roche P . Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells. Proc Natl Acad Sci U S A. 2015; 112(33):10449-54. PMC: 4547296. DOI: 10.1073/pnas.1507981112. View

11.

Mori Y, Matsui T, Furutani Y, Yoshihara Y, Fukuda M . Small GTPase Rab17 regulates dendritic morphogenesis and postsynaptic development of hippocampal neurons. J Biol Chem. 2012; 287(12):8963-73. PMC: 3308742. DOI: 10.1074/jbc.M111.314385. View

12.

McGaha T, Chen Y, Ravishankar B, van Rooijen N, Karlsson M . Marginal zone macrophages suppress innate and adaptive immunity to apoptotic cells in the spleen. Blood. 2011; 117(20):5403-12. DOI: 10.1182/blood-2010-11-320028. View

13.

Evans A, Blackburn J, Yin C, Heit B . Quantitative Efferocytosis Assays. Methods Mol Biol. 2016; 1519:25-41. DOI: 10.1007/978-1-4939-6581-6_3. View

14.

Walseng E, Furuta K, Bosch B, Weih K, Matsuki Y, Bakke O . Ubiquitination regulates MHC class II-peptide complex retention and degradation in dendritic cells. Proc Natl Acad Sci U S A. 2010; 107(47):20465-70. PMC: 2996684. DOI: 10.1073/pnas.1010990107. View

15.

Das A, Ganesh K, Khanna S, Sen C, Roy S . Engulfment of apoptotic cells by macrophages: a role of microRNA-21 in the resolution of wound inflammation. J Immunol. 2014; 192(3):1120-9. PMC: 4358325. DOI: 10.4049/jimmunol.1300613. View

16.

Fairn G, Grinstein S . How nascent phagosomes mature to become phagolysosomes. Trends Immunol. 2012; 33(8):397-405. DOI: 10.1016/j.it.2012.03.003. View

17.

LUTCKE A, Jansson S, Parton R, Chavrier P, Valencia A, Huber L . Rab17, a novel small GTPase, is specific for epithelial cells and is induced during cell polarization. J Cell Biol. 1993; 121(3):553-64. PMC: 2119572. DOI: 10.1083/jcb.121.3.553. View

18.

Cui Y, Zhao Q, Gao C, Ding Y, Zeng Y, Ueda T . Activation of the Rab7 GTPase by the MON1-CCZ1 Complex Is Essential for PVC-to-Vacuole Trafficking and Plant Growth in Arabidopsis. Plant Cell. 2014; 26(5):2080-2097. PMC: 4079370. DOI: 10.1105/tpc.114.123141. View

19.

Sotomayor E, Borrello I, Rattis F, Cuenca A, Abrams J, Levitsky H . Cross-presentation of tumor antigens by bone marrow-derived antigen-presenting cells is the dominant mechanism in the induction of T-cell tolerance during B-cell lymphoma progression. Blood. 2001; 98(4):1070-7. DOI: 10.1182/blood.v98.4.1070. View

20.

Flannagan R, Cosio G, Grinstein S . Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nat Rev Microbiol. 2009; 7(5):355-66. DOI: 10.1038/nrmicro2128. View