Gulp1 controls Eph/ephrin trogocytosis and is important for cell rearrangements during development

Journal of Cell Biology - Tập 218 Số 10 - Trang 3455-3471 - 2019
Jingyi Gong1, Thomas N. Gaitanos1, Olivia Luu2, Yunyun Huang2, Louise Gaitanos1, Jana Lindner1, Rudolf Winklbauer2, Rüdiger Klein1
1Max Planck Institute of Neurobiology, Department of Molecules-Signaling-Development, Munich-Martinsried, Germany 1
2Department of Cell and Systems Biology, University of Toronto, Toronto, Canada 2

Tóm tắt

Trogocytosis, in which cells nibble away parts of neighboring cells, is an intercellular cannibalism process conserved from protozoa to mammals. Its underlying molecular mechanisms are not well understood and are likely distinct from phagocytosis, a process that clears entire cells. Bi-directional contact repulsion induced by Eph/ephrin signaling involves transfer of membrane patches and full-length Eph/ephrin protein complexes between opposing cells, resembling trogocytosis. Here, we show that the phagocytic adaptor protein Gulp1 regulates EphB/ephrinB trogocytosis to achieve efficient cell rearrangements of cultured cells and during embryonic development. Gulp1 mediates trogocytosis bi-directionally by dynamic engagement with EphB/ephrinB protein clusters in cooperation with the Rac-specific guanine nucleotide exchange factor Tiam2. Ultimately, Gulp1’s presence at the Eph/ephrin cluster is a prerequisite for recruiting the endocytic GTPase dynamin. These results suggest that EphB/ephrinB trogocytosis, unlike other trogocytosis events, uses a phagocytosis-like mechanism to achieve efficient membrane scission and engulfment.

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Tài liệu tham khảo

Abdu, 2016, Developmentally programmed germ cell remodelling by endodermal cell cannibalism, Nat. Cell Biol., 18, 1302, 10.1038/ncb3439

Arandjelovic, 2015, Phagocytosis of apoptotic cells in homeostasis, Nat. Immunol., 16, 907, 10.1038/ni.3253

Astin, 2010, Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells, Nat. Cell Biol., 12, 1194, 10.1038/ncb2122

Batlle, 2012, Molecular mechanisms of cell segregation and boundary formation in development and tumorigenesis, Cold Spring Harb. Perspect. Biol., 4, 10.1101/cshperspect.a008227

Cayuso, 2015, Mechanisms of boundary formation by Eph receptor and ephrin signaling, Dev. Biol., 401, 122, 10.1016/j.ydbio.2014.11.013

Cowan, 2001, The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals, Nature., 413, 174, 10.1038/35093123

Dopfer, 2011, A new vampire saga: the molecular mechanism of T cell trogocytosis, Immunity., 35, 151, 10.1016/j.immuni.2011.08.004

Evergren, 2018, Eps15R and clathrin regulate EphB2-mediated cell repulsion, Traffic., 19, 44, 10.1111/tra.12531

Flannagan, 2012, The cell biology of phagocytosis, Annu. Rev. Pathol., 7, 61, 10.1146/annurev-pathol-011811-132445

Freeman, 2014, Phagocytosis: receptors, signal integration, and the cytoskeleton, Immunol. Rev., 262, 193, 10.1111/imr.12212

Gaitanos, 2016, Tiam-Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is important for cell repulsion, J. Cell Biol., 214, 735, 10.1083/jcb.201512010

Gong, 2016, Exosomes mediate cell contact-independent ephrin-Eph signaling during axon guidance, J. Cell Biol., 214, 35, 10.1083/jcb.201601085

Huang, 1999, TCR-Mediated internalization of peptide-MHC complexes acquired by T cells, Science., 286, 952, 10.1126/science.286.5441.952

Joly, 2003, What is trogocytosis and what is its purpose?, Nat. Immunol., 4, 815, 10.1038/ni0903-815

Kania, 2016, Mechanisms of ephrin-Eph signalling in development, physiology and disease, Nat. Rev. Mol. Cell Biol., 17, 240, 10.1038/nrm.2015.16

Kida, 2007, Daam1 regulates the endocytosis of EphB during the convergent extension of the zebrafish notochord, Proc. Natl. Acad. Sci. USA., 104, 6708, 10.1073/pnas.0608946104

Kinchen, 2005, Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans, Nature., 434, 93, 10.1038/nature03263

Koeppen, 2018, Functional Consequences of Synapse Remodeling Following Astrocyte-Specific Regulation of Ephrin-B1 in the Adult Hippocampus, J. Neurosci., 38, 5710, 10.1523/JNEUROSCI.3618-17.2018

Koizumi, 2018, New roles of reactive astrocytes in the brain; an organizer of cerebral ischemia, Neurochem. Int., 119, 107, 10.1016/j.neuint.2018.01.007

Lauterbach, 2006, Release of full-length EphB2 receptors from hippocampal neurons to cocultured glial cells, J. Neurosci., 26, 11575, 10.1523/JNEUROSCI.2697-06.2006

Li, 2012, SLIC: a method for sequence- and ligation-independent cloning, Methods Mol. Biol., 852, 51, 10.1007/978-1-61779-564-0_5

Lim, 2017, Diversity and Versatility of Phagocytosis: Roles in Innate Immunity, Tissue Remodeling, and Homeostasis, Front. Cell. Infect. Microbiol., 7, 191, 10.3389/fcimb.2017.00191

Lisabeth, 2013, Eph receptor signaling and ephrins, Cold Spring Harb. Perspect. Biol., 5, 10.1101/cshperspect.a009159

Liu, 1998, Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans, Cell., 93, 961, 10.1016/S0092-8674(00)81202-7

Marston, 2003, Rac-dependent trans-endocytosis of ephrinBs regulates Eph-ephrin contact repulsion, Nat. Cell Biol., 5, 879, 10.1038/ncb1044

Martínez-Martín, 2011, T cell receptor internalization from the immunological synapse is mediated by TC21 and RhoG GTPase-dependent phagocytosis, Immunity., 35, 208, 10.1016/j.immuni.2011.06.003

Nieuwkoop, 1967, Normal Table of Xenopus laevis (Daudin).

Parker, 2004, Reverse endocytosis of transmembrane ephrin-B ligands via a clathrin-mediated pathway, Biochem. Biophys. Res. Commun., 323, 17, 10.1016/j.bbrc.2004.07.209

Ralston, 2015, Taking a bite: Amoebic trogocytosis in Entamoeba histolytica and beyond, Curr. Opin. Microbiol., 28, 26, 10.1016/j.mib.2015.07.009

Ralston, 2014, Trogocytosis by Entamoeba histolytica contributes to cell killing and tissue invasion, Nature., 508, 526, 10.1038/nature13242

Riccomagno, 2015, Sculpting neural circuits by axon and dendrite pruning, Annu. Rev. Cell Dev. Biol., 31, 779, 10.1146/annurev-cellbio-100913-013038

Schaupp, 2014, The composition of EphB2 clusters determines the strength in the cellular repulsion response, J. Cell Biol., 204, 409, 10.1083/jcb.201305037

Session, 2016, Genome evolution in the allotetraploid frog Xenopus laevis, Nature., 538, 336, 10.1038/nature19840

Somlata, 2017, AGC family kinase 1 participates in trogocytosis but not in phagocytosis in Entamoeba histolytica, Nat. Commun., 8, 101, 10.1038/s41467-017-00199-y

Su, 2002, Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP), J. Biol. Chem., 277, 11772, 10.1074/jbc.M109336200

Sullivan, 2014, The adaptor protein GULP promotes Jedi-1-mediated phagocytosis through a clathrin-dependent mechanism, Mol. Biol. Cell., 25, 1925, 10.1091/mbc.e13-11-0658

Taylor, 2017, Ephs and ephrins, Curr. Biol., 27, R90, 10.1016/j.cub.2017.01.003

Ventrella, 2017, Asymmetry at cell-cell interfaces direct cell sorting, boundary formation, and tissue morphogenesis, Exp. Cell Res., 358, 58, 10.1016/j.yexcr.2017.03.024

Weinhard, 2018, Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction, Nat. Commun., 9, 1228, 10.1038/s41467-018-03566-5

Wen, 2017, Ingression-type cell migration drives vegetal endoderm internalisation in the Xenopus gastrula, eLife., 6, 10.7554/eLife.27190

Winklbauer, 1988, Differential interaction of Xenopus embryonic cells with fibronectin in vitro, Dev. Biol., 130, 175, 10.1016/0012-1606(88)90424-1

Winklbauer, 1999, Vegetal rotation, a new gastrulation movement involved in the internalization of the mesoderm and endoderm in Xenopus, Development., 126, 3703, 10.1242/dev.126.16.3703

Xu, 2009, Ephrin-B3 reverse signaling through Grb4 and cytoskeletal regulators mediates axon pruning, Nat. Neurosci., 12, 268, 10.1038/nn.2254

Yu, 2006, C. elegans Dynamin mediates the signaling of phagocytic receptor CED-1 for the engulfment and degradation of apoptotic cells, Dev. Cell., 10, 743, 10.1016/j.devcel.2006.04.007

Zhang, 2014, An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex, J. Neurosci., 34, 11929, 10.1523/JNEUROSCI.1860-14.2014

Zimmer, 2003, EphB-ephrinB bi-directional endocytosis terminates adhesion allowing contact mediated repulsion, Nat. Cell Biol., 5, 869, 10.1038/ncb1045