Clathrin and AP2 Are Required for Phagocytic Receptor-Mediated Apoptotic Cell Clearance in

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Clathrin and the multi-subunit adaptor protein complex AP2 are central players in clathrin-mediated endocytosis by which the cell selectively internalizes surface materials. Here, we report the essential role of clathrin and AP2 in phagocytosis of apoptotic cells. In Caenorhabditis elegans, depletion of the clathrin heavy chain CHC-1 and individual components of AP2 led to a significant accumulation of germ cell corpses, which resulted from defects in both cell corpse engulfment and phagosome maturation required for corpse removal. CHC-1 and AP2 components associate with phagosomes in an inter-dependent manner. Importantly, we found that the phagocytic receptor CED-1 interacts with the α subunit of AP2, while the CED-6/Gulp adaptor forms a complex with both CHC-1 and the AP2 complex, which likely mediates the rearrangement of the actin cytoskeleton required for cell corpse engulfment triggered by the CED-1 signaling pathway. In addition, CHC-1 and AP2 promote the phagosomal association of LST-4/Snx9/18/33 and DYN-1/dynamin by forming a complex with them, thereby facilitating the maturation of phagosomes necessary for corpse degradation. These findings reveal a non-classical role of clathrin and AP2 and establish them as indispensable regulators in phagocytic receptor-mediated apoptotic cell clearance.

Vyšlo v časopise: Clathrin and AP2 Are Required for Phagocytic Receptor-Mediated Apoptotic Cell Clearance in. PLoS Genet 9(5): e32767. doi:10.1371/journal.pgen.1003517
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003517

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1. SavillJ, DransfieldI, GregoryC, HaslettC (2002) A blast from the past: clearance of apoptotic cells regulates immune responses. Nat Rev Immunol 2: 965–975.

2. HensonPM, BrattonDL, FadokVA (2001) Apoptotic cell removal. Curr Biol 11: R795–805.

3. ReddienPW, HorvitzHR (2004) The Engulfment Process of Programmed Cell Death in Caenorhabditis elegans. Annu Rev Cell Dev Biol

4. WangX, WuYC, FadokVA, LeeMC, Gengyo-AndoK, et al. (2003) Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12. Science 302: 1563–1566.

5. ReddienPW, HorvitzHR (2000) CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans. Nat Cell Biol 2: 131–136.

6. WuYC, HorvitzHR (1998) C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180. Nature 392: 501–504.

7. WuYC, TsaiMC, ChengLC, ChouCJ, WengNY (2001) C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment. Dev Cell 1: 491–502.

8. deBakkerCD, HaneyLB, KinchenJM, GrimsleyC, LuM, et al. (2004) Phagocytosis of apoptotic cells is regulated by a UNC-73/TRIO-MIG-2/RhoG signaling module and armadillo repeats of CED-12/ELMO. Curr Biol 14: 2208–2216.

9. HsuTY, WuYC (2010) Engulfment of apoptotic cells in C. elegans is mediated by integrin alpha/SRC signaling. Curr Biol 20: 477–486.

10. CabelloJ, NeukommLJ, GunesdoganU, BurkartK, CharetteSJ, et al. (2010) The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac. PLoS Biol 8: e1000297 doi:10.1371/journal.pbio.1000297.

11. ZhouZ, HartwiegE, HorvitzHR (2001) CED-1 is a transmembrane receptor that mediates cell corpse engulfment in C. elegans. Cell 104: 43–56.

12. ManakaJ, KuraishiT, ShiratsuchiA, NakaiY, HigashidaH, et al. (2004) Draper-mediated and phosphatidylserine-independent phagocytosis of apoptotic cells by Drosophila hemocytes/macrophages. J Biol Chem 279: 48466–48476.

13. HamonY, TrompierD, MaZ, VenegasV, PophillatM, et al. (2006) Cooperation between engulfment receptors: the case of ABCA1 and MEGF10. PLoS ONE 1: e120 doi:10.1371/journal.pone.0000120.

14. SuHP, Nakada-TsukuiK, Tosello-TrampontAC, LiY, BuG, et al. (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: 11772–11779.

15. KurantE, AxelrodS, LeamanD, GaulU (2008) Six-microns-under acts upstream of Draper in the glial phagocytosis of apoptotic neurons. Cell 133: 498–509.

16. WangX, LiW, ZhaoD, LiuB, ShiY, et al. (2010) Caenorhabditis elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor. Nat Cell Biol 12: 655–664.

17. LiuQA, HengartnerMO (1998) Candidate adaptor protein CED-6 promotes the engulfment of apoptotic cells in C. elegans. Cell 93: 961–972.

18. YuX, OderaS, ChuangCH, LuN, ZhouZ (2006) C. elegans Dynamin mediates the signaling of phagocytic receptor CED-1 for the engulfment and degradation of apoptotic cells. Dev Cell 10: 743–757.

19. WuYC, HorvitzHR (1998) The C. elegans cell corpse engulfment gene ced-7 encodes a protein similar to ABC transporters. Cell 93: 951–960.

20. ZhangY, WangH, Kage-NakadaiE, MitaniS, WangX (2012) C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment. Curr Biol 22: 1276–1284.

21. MapesJ, ChenYZ, KimA, MitaniS, KangBH, et al. (2012) CED-1, CED-7, and TTR-52 regulate surface phosphatidylserine expression on apoptotic and phagocytic cells. Curr Biol 22: 1267–1275.

22. ChenD, XiaoH, ZhangK, WangB, GaoZ, et al. (2010) Retromer is required for apoptotic cell clearance by phagocytic receptor recycling. Science 327: 1261–1264.

23. KinchenJM, DoukoumetzidisK, AlmendingerJ, StergiouL, Tosello-TrampontA, et al. (2008) A pathway for phagosome maturation during engulfment of apoptotic cells. Nat Cell Biol 10: 556–566.

24. SumakovicM, HegermannJ, LuoL, HussonSJ, SchwarzeK, et al. (2009) UNC-108/RAB-2 and its effector RIC-19 are involved in dense core vesicle maturation in Caenorhabditis elegans. J Cell Biol 186: 897–914.

25. LuQ, ZhangY, HuT, GuoP, LiW, et al. (2008) C. elegans Rab GTPase 2 is required for the degradation of apoptotic cells. Development 135: 1069–1080.

26. YuX, LuN, ZhouZ (2008) Phagocytic receptor CED-1 initiates a signaling pathway for degrading engulfed apoptotic cells. PLoS Biol 6: e61 doi:10.1371/journal.pbio.0060061.

27. GuoP, HuT, ZhangJ, JiangS, WangX (2010) Sequential action of Caenorhabditis elegans Rab GTPases regulates phagolysosome formation during apoptotic cell degradation. Proc Natl Acad Sci U S A 107: 18016–18021.

28. LiW, ZouW, ZhaoD, YanJ, ZhuZ, et al. (2009) C. elegans Rab GTPase activating protein TBC-2 promotes cell corpse degradation by regulating the small GTPase RAB-5. Development 136: 2445–2455.

29. XiaoH, ChenD, FangZ, XuJ, SunX, et al. (2009) Lysosome biogenesis mediated by vps-18 affects apoptotic cell degradation in Caenorhabditis elegans. Mol Biol Cell 20: 21–32.

30. KinchenJM, RavichandranKS (2008) Phagosome maturation: going through the acid test. Nat Rev Mol Cell Biol 9: 781–795.

31. DohertyGJ, McMahonHT (2009) Mechanisms of endocytosis. Annu Rev Biochem 78: 857–902.

32. McMahonHT, BoucrotE (2011) Molecular mechanism and physiological functions of clathrin-mediated endocytosis. Nat Rev Mol Cell Biol 12: 517–533.

33. TraubLM (2009) Tickets to ride: selecting cargo for clathrin-regulated internalization. Nat Rev Mol Cell Biol 10: 583–596.

34. VeigaE, CossartP (2005) Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat Cell Biol 7: 894–900.

35. SatoK, ErnstromGG, WatanabeS, WeimerRM, ChenCH, et al. (2009) Differential requirements for clathrin in receptor-mediated endocytosis and maintenance of synaptic vesicle pools. Proc Natl Acad Sci U S A 106: 1139–1144.

36. AlmendingerJ, DoukoumetzidisK, KinchenJM, KaechA, RavichandranKS, et al. (2011) A conserved role for SNX9-family members in the regulation of phagosome maturation during engulfment of apoptotic cells. PLoS ONE 6: e18325 doi:10.1371/journal.pone.0018325.

37. LundmarkR, CarlssonSR (2009) SNX9 - a prelude to vesicle release. J Cell Sci 122: 5–11.

38. KritikouEA, MilsteinS, VidalainPO, LettreG, BoganE, et al. (2006) C. elegans GLA-3 is a novel component of the MAP kinase MPK-1 signaling pathway required for germ cell survival. Genes Dev 20: 2279–2292.

39. EdwardsKA, DemskyM, MontagueRA, WeymouthN, KiehartDP (1997) GFP-moesin illuminates actin cytoskeleton dynamics in living tissue and demonstrates cell shape changes during morphogenesis in Drosophila. Dev Biol 191: 103–117.

40. SouletF, YararD, LeonardM, SchmidSL (2005) SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell 16: 2058–2067.

41. LundmarkR, CarlssonSR (2003) Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components. J Biol Chem 278: 46772–46781.

42. LuN, ShenQ, MahoneyTR, LiuX, ZhouZ (2011) Three sorting nexins drive the degradation of apoptotic cells in response to PtdIns(3)P signaling. Mol Biol Cell 22: 354–374.

43. YangC, YanN, ParishJ, WangX, ShiY, et al. (2006) RNA aptamers targeting the cell death inhibitor CED-9 induce cell killing in Caenorhabditis elegans. J Biol Chem 281: 9137–9144.

44. KinchenJM, CabelloJ, KlingeleD, WongK, FeichtingerR, et al. (2005) Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans. Nature 434: 93–99.

45. BrodskyFM (2012) Diversity of clathrin function: new tricks for an old protein. Annu Rev Cell Dev Biol 28: 309–336.

46. VeigaE, GuttmanJA, BonazziM, BoucrotE, Toledo-AranaA, et al. (2007) Invasive and adherent bacterial pathogens co-Opt host clathrin for infection. Cell Host Microbe 2: 340–351.

47. EtoDS, GordonHB, DhakalBK, JonesTA, MulveyMA (2008) Clathrin, AP-2, and the NPXY-binding subset of alternate endocytic adaptors facilitate FimH-mediated bacterial invasion of host cells. Cell Microbiol 10: 2553–2567.

48. ChanYG, CardwellMM, HermanasTM, UchiyamaT, MartinezJJ (2009) Rickettsial outer-membrane protein B (rOmpB) mediates bacterial invasion through Ku70 in an actin, c-Cbl, clathrin and caveolin 2-dependent manner. Cell Microbiol 11: 629–644.

49. Moreno-RuizE, Galan-DiezM, ZhuW, Fernandez-RuizE, d'EnfertC, et al. (2009) Candida albicans internalization by host cells is mediated by a clathrin-dependent mechanism. Cell Microbiol 11: 1179–1189.

50. CuretonDK, MassolRH, SaffarianS, KirchhausenTL, WhelanSP (2009) Vesicular stomatitis virus enters cells through vesicles incompletely coated with clathrin that depend upon actin for internalization. PLoS Pathog 5: e1000394 doi:10.1371/journal.ppat.1000394.

51. BonazziM, VasudevanL, MalletA, SachseM, SartoriA, et al. (2011) Clathrin phosphorylation is required for actin recruitment at sites of bacterial adhesion and internalization. J Cell Biol 195: 525–536.

52. NakayamaM, KikunoR, OharaO (2002) Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs. Genome Res 12: 1773–1784.

53. SuzukiE, NakayamaM (2007) The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion pattern. Exp Cell Res 313: 2451–2464.

54. JhaA, WatkinsSC, TraubLM The apoptotic engulfment protein Ced-6 participates in clathrin-mediated yolk uptake in Drosophila egg chambers. Mol Biol Cell 23: 1742–1764.

55. Martins-SilvaC, FerreiraLT, CyrM, KoenenJ, FernandesDR, et al. (2006) A rat homologue of CED-6 is expressed in neurons and interacts with clathrin. Brain Res 1119: 1–12.

56. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.

57. MelloCC, KramerJM, StinchcombD, AmbrosV (1991) Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. Embo J 10: 3959–3970.

58. ZielJW, HagedornEJ, AudhyaA, SherwoodDR (2009) UNC-6 (netrin) orients the invasive membrane of the anchor cell in C. elegans. Nat Cell Biol 11: 183–189.

59. WangX, YangC, ChaiJ, ShiY, XueD (2002) Mechanisms of AIF-mediated apoptotic DNA degradation in Caenorhabditis elegans. Science 298: 1587–1592.

60. GumiennyTL, LambieE, HartwiegE, HorvitzHR, HengartnerMO (1999) Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development 126: 1011–1022.