Regulation of phagocytosis by TAM receptors and their ligands

Qingxian LU, Qiutang LI, Qingjun LU

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Front. Biol. ›› 2010, Vol. 5 ›› Issue (3) : 227-237. DOI: 10.1007/s11515-010-0034-5
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Regulation of phagocytosis by TAM receptors and their ligands

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Abstract

The TAM family of receptors is preferentially expressed by professional and non-professional phagocytes, including macrophages, dendritic cells and natural killer cells in the immune system, osteoclasts in bone, Sertoli cells in testis, and retinal pigmental epithelium cells in the retina. Mutations in the Mertk single gene or in different combinations of the double or triple gene mutations in the same cell cause complete or partial impairment in phagocytosis of their preys; and as a result, either the normal apoptotic cells cannot be efficiently removed or the tissue neighbor cells die by apoptosis. This scenario of TAM regulation represents a widely adapted model system used by phagocytes in all different tissues. The present review will summarize current known functional roles of TAM receptors and their ligands, Gas 6 and protein S, in the regulation of phagocytosis.

Keywords

TAM family (Tyro3, Axl and Mertk) / ligands / growth-arrest specific gene 6 (Gas 6) / protein S / regulation / phagocytosis

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Qingxian LU, Qiutang LI, Qingjun LU. Regulation of phagocytosis by TAM receptors and their ligands. Front Biol, 2010, 5(3): 227‒237 https://doi.org/10.1007/s11515-010-0034-5

References

[1]
Ait-Oufella H, Pouresmail V, Simon T, Blanc-Brude O, Kinugawa K, Merval R, Offenstadt G, Lesèche G, Cohen P L, Tedgui A, Mallat Z (2008). Defective mer receptor tyrosine kinase signaling in bone marrow cells promotes apoptotic cell accumulation and accelerates atherosclerosis. Arterioscler Thromb Vasc Biol, 28(8): 1429-1431
CrossRef Google scholar
[2]
Anderson H A, Maylock C A, Williams J A, Paweletz C P, Shu H, Shacter E (2003). Serum-derived protein S binds to phosphatidylserine and stimulates the phagocytosis of apoptotic cells. Nat Immunol, 4(1): 87-91
CrossRef Google scholar
[3]
Angelillo-Scherrer A, de Frutos P, Aparicio C, Melis E, Savi P, Lupu F, Arnout J, Dewerchin M, Hoylaerts M, Herbert J, Collen D, Dahlbäck B, Carmeliet P (2001). Deficiency or inhibition of Gas6 causes platelet dysfunction and protects mice against thrombosis. Nat Med, 7(2): 215-221
CrossRef Google scholar
[4]
Araki N, Johnson M T, Swanson J A (1996). A role for phosphoinositide 3-kinase in the completion of macropinocytosis and phagocytosis by macrophages. J Cell Biol, 135(5): 1249-1260
CrossRef Google scholar
[5]
Bellosta P, Zhang Q, Goff S P, Basilico C (1997). Signaling through the ARK tyrosine kinase receptor protects from apoptosis in the absence of growth stimulation. Oncogene, 15(20): 2387-2397
CrossRef Google scholar
[6]
Bernstein P S, Law W C, Rando R R (1987). Biochemical characterization of the retinoid isomerase system of the eye. J Biol Chem, 262(35): 16848-16857
[7]
Bok D, Hall M O (1971). The role of the pigment epithelium in the etiology of inherited retinal dystrophy in the rat. J Cell Biol, 49(3): 664-682
CrossRef Google scholar
[8]
Braunger J, Schleithoff L, Schulz A S, Kessler H, Lammers R, Ullrich A, Bartram C R, Janssen J W (1997). Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. Oncogene, 14(22): 2619-2631
CrossRef Google scholar
[9]
Burstyn-Cohen T, Heeb MJ, Lemke G (2009). Lack of protein S in mice causes embryonic lethal coagulopathy and vascular dysgenesis. J Clin Invest, 119(10): 2942-2953
CrossRef Google scholar
[10]
Camenisch T D, Koller B H, Earp H S, Matsushima G K (1999). A novel receptor tyrosine kinase, Mer, inhibits TNF-alpha production and lipopolysaccharide-induced endotoxic shock. J Immunol, 162(6): 3498-3503
[11]
Caraux A, Lu Q, Fernandez N, Riou S, Di Santo J P, Raulet D H, Lemke G, Roth C (2006). Natural killer cell differentiation driven by Tyro3 receptor tyrosine kinases. Nat Immunol, 7(7): 747-754
CrossRef Google scholar
[12]
Charbel Issa P, Bolz H J, Ebermann I, Domeier E, Holz F G, Scholl H P (2009). Characterisation of severe rod-cone dystrophy in a consanguineous family with a splice site mutation in the MERTK gene. Br J Ophthalmol, 93(7): 920-925
CrossRef Google scholar
[13]
Chen J, Carey K, Godowski P J (1997). Identification of Gas6 as a ligand for Mer, a neural cell adhesion molecule related receptor tyrosine kinase implicated in cellular transformation. Oncogene, 14(17): 2033-2039
CrossRef Google scholar
[14]
D’Angelo A, Viganò D’Angelo S (2008). Protein S deficiency. Haematologica, 93(4): 498-501
CrossRef Google scholar
[15]
D’Cruz P M, Yasumura D, Weir J, Matthes M T, Abderrahim H, LaVail M M, Vollrath D (2000). Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet, 9(4): 645-651
CrossRef Google scholar
[16]
Dahlbäck B (1991). Protein S and C4b-binding protein: components involved in the regulation of the protein C anticoagulant system. Thromb Haemost, 66(1): 49-61
[17]
Dowling J E, Sidman R L (1962). Inherited retinal dystrophy in the rat. J Cell Biol, 14: 73-109
CrossRef Google scholar
[18]
Duncan J L, LaVail M M, Yasumura D, Matthes M T, Yang H, Trautmann N, Chappelow A V, Feng W, Earp H S, Matsushima G K, Vollrath D (2003a). An RCS-like retinal dystrophy phenotype in mer knockout mice. Invest Ophthalmol Vis Sci, 44(2): 826-838
CrossRef Google scholar
[19]
Duncan J L, Yang H, Vollrath D, Yasumura D, Matthes M T, Trautmann N, Chappelow A V, Feng W, Earp H S, Matsushima G K, LaVail M M (2003b). Inherited retinal dystrophy in Mer knockout mice. Adv Exp Med Biol, 533: 165-172
[20]
Edwards R B, Szamier R B (1977). Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture. Science, 197(4307): 1001-1003
CrossRef Google scholar
[21]
Feng W, Yasumura D, Matthes M T, LaVail M M, Vollrath D (2002). Mertk triggers uptake of photoreceptor outer segments during phagocytosis by cultured retinal pigment epithelial cells. J Biol Chem, 277(19): 17016-17022
CrossRef Google scholar
[22]
Finnemann S C (2003). Focal adhesion kinase signaling promotes phagocytosis of integrin-bound photoreceptors. EMBO J, 22(16): 4143-4154
CrossRef Google scholar
[23]
Finnemann S C, Rodriguez-Boulan E (1999). Macrophage and retinal pigment epithelium phagocytosis: apoptotic cells and photoreceptors compete for alphavbeta3 and alphavbeta5 integrins, and protein kinase C regulates alphavbeta5 binding and cytoskeletal linkage. J Exp Med, 190(6): 861-874
CrossRef Google scholar
[24]
Gal A, Li Y, Thompson D A, Weir J, Orth U, Jacobson S G, Apfelstedt-Sylla E, Vollrath D (2000). Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet, 26(3): 270-271
CrossRef Google scholar
[25]
García de Frutos P, Fuentes-Prior P, Hurtado B, Sala N (2007). Molecular basis of protein S deficiency. Thromb Haemost, 98(3): 543-556
[26]
Georgescu M M, Kirsch K H, Shishido T, Zong C, Hanafusa H (1999). Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB. Mol Cell Biol, 19(2): 1171-1181
[27]
Godowski P J, Mark M R, Chen J, Sadick M D, Raab H, Hammonds R G (1995). Reevaluation of the roles of protein S and Gas6 as ligands for the receptor tyrosine kinase Rse/Tyro 3. Cell, 82(3): 355-358
CrossRef Google scholar
[28]
Graham D K, Dawson T L, Mullaney D L, Snodgrass H R, Earp H S (1994). Cloning and mRNA expression analysis of a novel human protooncogene, c-mer. Cell Growth Differ, 5(6): 647-657
[29]
Hafizi S, Dahlbäck B (2006). Signalling and functional diversity within the Axl subfamily of receptor tyrosine kinases. Cytokine Growth Factor Rev, 17(4): 295-304
CrossRef Google scholar
[30]
Hall M O, Abrams T (1987). Kinetic studies of rod outer segment binding and ingestion by cultured rat RPE cells. Exp Eye Res, 45(6): 907-922
CrossRef Google scholar
[33]
Hall M O, Agnew B J, Abrams T A, Burgess B L (2003). The phagocytosis of os is mediated by the PI3-kinase linked tyrosine kinase receptor, mer, and is stimulated by GAS6. Adv Exp Med Biol, 533: 331-336
[34]
Hall M O, Obin M S, Heeb M J, Burgess B L, Abrams T A (2005). Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat retinal pigment epithelial cells. Exp Eye Res, 81(5): 581-591
CrossRef Google scholar
[32]
Hall M O, Obin M S, Prieto A L, Burgess B L, Abrams T A (2002). Gas6 binding to photoreceptor outer segments requires gamma-carboxyglutamic acid (Gla) and Ca(2+) and is required for OS phagocytosis by RPE cells in vitro. Exp Eye Res, 75(4): 391-400
CrossRef Google scholar
[31]
Hall M O, Prieto A L, Obin M S, Abrams T A, Burgess B L, Heeb M J, Agnew B J (2001). Outer segment phagocytosis by cultured retinal pigment epithelial cells requires Gas6. Exp Eye Res, 73(4): 509-520
CrossRef Google scholar
[35]
Hasanbasic I, Rajotte I, Blostein M (2005). The role of gamma-carboxylation in the anti-apoptotic function of gas6. J Thromb Haemost, 3(12): 2790-2797
CrossRef Google scholar
[36]
Huang M, Rigby A C, Morelli X, Grant M A, Huang G, Furie B, Seaton B, Furie B C (2003). Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins. Nat Struct Biol, 10(9): 751-756
CrossRef Google scholar
[38]
Hubbard S R, Mohammadi M, Schlessinger J (1998). Autoregulatory mechanisms in protein-tyrosine kinases. J Biol Chem, 273(20): 11987-11990
CrossRef Google scholar
[37]
Hubbard S R, Till J H (2000). Protein tyrosine kinase structure and function. Annu Rev Biochem, 69: 373-398
CrossRef Google scholar
[39]
Ishimoto Y, Ohashi K, Mizuno K, Nakano T (2000). Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6. J Biochem, 127(3): 411-417
[40]
Janssen J W, Schulz A S, Steenvoorden A C, Schmidberger M, Strehl S, Ambros P F, Bartram C R (1991). A novel putative tyrosine kinase receptor with oncogenic potential. Oncogene, 6(11): 2113-2120
[41]
Jia R, Hanafusa H (1994). The proto-oncogene of v-eyk (v-ryk) is a novel receptor-type protein tyrosine kinase with extracellular Ig/GN-III domains. J Biol Chem, 269(3): 1839-1844
[42]
Kamen L A, Levinsohn J, Swanson J A (2007). Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with forming phagosomes. Mol Biol Cell. 8(7): 2463-2472
CrossRef Google scholar
[43]
Keating A K, Salzberg D B, Sather S, Liang X, Nickoloff S, Anwar A, Deryckere D, Hill K, Joung D, Sawczyn K K, Park J, Curran-Everett D, McGavran L, Meltesen L, Gore L, Johnson G L, Graham D K (2006). Lymphoblastic leukemia/lymphoma in mice overexpressing the Mer (MerTK) receptor tyrosine kinase. Oncogene, 25(45): 6092-6100
CrossRef Google scholar
[44]
Lai C, Gore M, Lemke G (1994). Structure, expression, and activity of Tyro 3, a neural adhesion-related receptor tyrosine kinase. Oncogene, 9(9): 2567-2578
[45]
LaVail M M (1973). Kinetics of rod outer segment renewal in the developing mouse retina. J Cell Biol, 58(3): 650-661
CrossRef Google scholar
[46]
LaVail M M (1976). Rod outer segment disk shedding in rat retina: relationship to cyclic lighting. Science, 194(4269): 1071-1074
CrossRef Google scholar
[47]
Lemke G, Lu Q (2003). Macrophage regulation by Tyro 3 family receptors. Curr Opin Immunol, 15(1): 31-36
CrossRef Google scholar
[48]
Lemke G, Rothlin C V (2008). Immunobiology of the TAM receptors. Nat Rev Immunol, 8(5): 327-336
CrossRef Google scholar
[50]
Lu Q, Gore M, Zhang Q, Camenisch T, Boast S, Casagranda F, Lai C, Skinner M K, Klein R, Matsushima G K, Earp H S, Goff S P, Lemke G (1999). Tyro-3 family receptors are essential regulators of mammalian spermatogenesis. Nature, 398(6729): 723-728
CrossRef Google scholar
[49]
Lu Q, Lemke G (2001). Homeostatic regulation of the immune system by receptor tyrosine kinases of the Tyro 3 family. Science, 293(5528): 306-311
CrossRef Google scholar
[51]
Lundwall A, Dackowski W, Cohen E, Shaffer M, Mahr A, Dahlbäck B, Stenflo J, Wydro R (1986). Isolation and sequence of the cDNA for human protein S, a regulator of blood coagulation. Proc Natl Acad Sci U S A, 83(18): 6716-6720
CrossRef Google scholar
[52]
Maeda Y, Shiratsuchi A, Namiki M, Nakanishi Y (2002). Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Cell Death Differ, 9(7): 742-749
CrossRef Google scholar
[53]
Maguire A M, Simonelli F, Pierce E A, Pugh E N Jr, Mingozzi F, Bennicelli J, Banfi S, Marshall K A, Testa F, Surace E M, Rossi S, Lyubarsky A, Arruda V R, Konkle B, Stone E, Sun J, Jacobs J, Dell’Osso L, Hertle R, Ma J X, Redmond T M, Zhu X, Hauck B, Zelenaia O, Shindler K S, Maguire M G, Wright J F, Volpe N J, McDonnell J W, Auricchio A, High K A, Bennett J (2008). Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med, 358(21): 2240-2248
CrossRef Google scholar
[54]
Mahajan N P, Earp H S (2003). An SH2 domain-dependent, phosphotyrosine-independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J Biol Chem, 278(43): 42596-42603
CrossRef Google scholar
[55]
Manfioletti G, Brancolini C, Avanzi G, Schneider C (1993). The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade. Mol Cell Biol, 13(8): 4976-4985
[56]
Manning G, Whyte D B, Martinez R, Hunter T, Sudarsanam S (2002). The protein kinase complement of the human genome. Science, 298(5600): 1912-1934
CrossRef Google scholar
[57]
Mark M R, Chen J, Hammonds R G, Sadick M, Godowsk P J (1996). Characterization of Gas6, a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl. J Biol Chem, 271(16): 9785-9789
CrossRef Google scholar
[58]
May R C, Machesky L M (2001). Phagocytosis and the actin cytoskeleton. J Cell Sci, 114(Pt 6): 1061-1077
[59]
Mayerson P L, Hall M O (1986). Rat retinal pigment epithelial cells show specificity of phagocytosis in vitro. J Cell Biol, 103(1): 299-308
CrossRef Google scholar
[60]
Mays R W, Beck K A, Nelson W J (1994). Organization and function of the cytoskeleton in polarized epithelial cells: a component of the protein sorting machinery. Curr Opin Cell Biol, 6(1): 16-24
CrossRef Google scholar
[61]
McHenry C L, Liu Y, Feng W, Nair A R, Feathers K L, Ding X, Gal A, Vollrath D, Sieving P A, Thompson D A (2004). MERTK arginine-844-cysteine in a patient with severe rod-cone dystrophy: loss of mutant protein function in transfected cells. Invest Ophthalmol Vis Sci, 45(5): 1456-1463
CrossRef Google scholar
[62]
Miething A (1992). Germ-cell death during prespermatogenesis in the testis of the golden hamster. Cell Tissue Res, 267(3): 583-590
CrossRef Google scholar
[63]
Miljanich G P, Nemes P P, White D L, Dratz E A (1981). The asymmetric transmembrane distribution of phosphatidylethanolamine, phosphatidylserine, and fatty acids of the bovine retinal rod outer segment disk membrane. J Membr Biol, 60(3): 249-255
CrossRef Google scholar
[64]
Mullen R J, LaVail M M (1976). Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Science, 192(4241): 799-801
CrossRef Google scholar
[65]
Nagata K, Ohashi K, Nakano T, Arita H, Zong C, Hanafusa H, Mizuno K (1996). Identification of the product of growth arrest-specific gene 6 as a common ligand for Axl, Sky, and Mer receptor tyrosine kinases. J Biol Chem, 271(47): 30022-30027
CrossRef Google scholar
[67]
Nakano T, Ishimoto Y, Kishino J, Umeda M, Inoue K, Nagata K, Ohashi K, Mizuno K, Arita H (1997). Cell adhesion to phosphatidylserine mediated by a product of growth arrest-specific gene 6. J Biol Chem, 272(47): 29411-29414
CrossRef Google scholar
[66]
Nakano T, Kawamoto K, Kishino J, Nomura K, Higashino K, Arita H (1997). Requirement of gamma-carboxyglutamic acid residues for the biological activity of Gas6: contribution of endogenous Gas6 to the proliferation of vascular smooth muscle cells. Biochem J, 323(Pt 2): 387-392
[68]
Nandrot E, Dufour E M, Provost A C, Péquignot M O, Bonnel S, Gogat K, Marchant D, Rouillac C, Sépulchre de Condé B, Bihoreau M T, Shaver C, Dufier J L, Marsac C, Lathrop M, Menasche M, Abitbol M M (2000). Homozygous deletion in the coding sequence of the c-mer gene in RCS rats unravels general mechanisms of physiological cell adhesion and apoptosis. Neurobiol Dis, 7(6 Pt B): 586-599
CrossRef Google scholar
[70]
Nandrot E F, Anand M, Sircar M, Finnemann S C (2006). Novel role for alphavbeta5-integrin in retinal adhesion and its diurnal peak. Am J Physiol Cell Physiol, 290(4): C1256-C1262
CrossRef Google scholar
[69]
Nandrot E F, Kim Y, Brodie S E, Huang X, Sheppard D, Finnemann S C (2004). Loss of synchronized retinal phagocytosis and age-related blindness in mice lacking alphavbeta5 integrin. J Exp Med, 200(12): 1539-1545
CrossRef Google scholar
[71]
Niedergang F, Chavrier P (2004). Signaling and membrane dynamics during phagocytosis: many roads lead to the phagos(R)ome. Curr Opin Cell Biol, 16(4): 422-428
CrossRef Google scholar
[72]
O’Bryan J P, Frye R A, Cogswell P C, Neubauer A, Kitch B, Prokop C, Espinosa R 3rd, Le Beau M M, Earp H S, Liu E T (1991). axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase. Mol Cell Biol, 11(10): 5016-5031
[73]
Ohashi K, Mizuno K, Kuma K, Miyata T, Nakamura T (1994). Cloning of the cDNA for a novel receptor tyrosine kinase, Sky, predominantly expressed in brain. Oncogene, 9(3): 699-705
[74]
Prasad D, Rothlin C V, Burrola P, Burstyn-Cohen T, Lu Q, Garcia de Frutos P, Lemke G (2006). TAM receptor function in the retinal pigment epithelium. Mol Cell Neurosci, 33(1): 96-108
CrossRef Google scholar
[75]
Rescigno J, Mansukhani A, Basilico C (1991). A putative receptor tyrosine kinase with unique structural topology. Oncogene, 6(10): 1909-1913
[76]
Robinson D R, Wu Y M, Lin S F (2000). The protein tyrosine kinase family of the human genome. Oncogene, 19(49): 5548-5557
CrossRef Google scholar
[77]
Rothlin C V, Ghosh S, Zuniga E I, Oldstone M B, Lemke G (2007). TAM receptors are pleiotropic inhibitors of the innate immune response. Cell, 131(6): 1124-1136
CrossRef Google scholar
[78]
Saller F, Brisset A C, Tchaikovski S N, Azevedo M, Chrast R, Fernández J A, Schapira M, Hackeng T M, Griffin J H, Angelillo-Scherrer A (2009). Generation and phenotypic analysis of protein S-deficient mice. Blood, 114(11): 2307-2314
CrossRef Google scholar
[79]
Sasaki T, Knyazev P G, Cheburkin Y, Göhring W, Tisi D, Ullrich A, Timpl R, Hohenester E (2002). Crystal structure of a C-terminal fragment of growth arrest-specific protein Gas6. Receptor tyrosine kinase activation by laminin G-like domains. J Biol Chem, 277(46): 44164-44170
CrossRef Google scholar
[80]
Sasaki T, Knyazev P G, Clout N J, Cheburkin Y, Göhring W, Ullrich A, Timpl R, Hohenester E (2006). Structural basis for Gas6-Axl signalling. EMBO J, 25(1): 80-87
CrossRef Google scholar
[81]
Sather S, Kenyon K D, Lefkowitz J B, Liang X, Varnum B C, Henson P M, Graham D K (2007). A soluble form of the Mer receptor tyrosine kinase inhibits macrophage clearance of apoptotic cells and platelet aggregation. Blood, 109(3): 1026-1033
CrossRef Google scholar
[82]
Schlessinger J (2000). Cell signaling by receptor tyrosine kinases. Cell, 103(2): 211-225
CrossRef Google scholar
[83]
Schneider C, King R M, Philipson L (1988). Genes specifically expressed at growth arrest of mammalian cells. Cell, 54(6): 787-793
CrossRef Google scholar
[84]
Scott R S, McMahon E J, Pop S M, Reap E A, Caricchio R, Cohen P L, Earp H S, Matsushima G K (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature, 411(6834): 207-211
CrossRef Google scholar
[85]
Seitz H M, Camenisch T D, Lemke G, Earp H S, Matsushima G K (2007). Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J Immunol, 178(9): 5635-5642
[86]
Sen P, Wallet M A, Yi Z, Huang Y, Henderson M, Mathews C E, Earp H S, Matsushima G, Baldwin A S Jr, Tisch R M (2007). Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood, 109(2): 653-660
CrossRef Google scholar
[87]
Shankar S L, O’Guin K, Cammer M, McMorris F A, Stitt T N, Basch R S, Varnum B, Shafit-Zagardo B (2003). The growth arrest-specific gene product Gas6 promotes the survival of human oligodendrocytes via a phosphatidylinositol 3-kinase-dependent pathway. J Neurosci, 23(10): 4208-4218
[88]
Shankar S L, O’Guin K, Kim M, Varnum B, Lemke G, Brosnan C F, Shafit-Zagardo B (2006). Gas6/Axl signaling activates the phosphatidylinositol 3-kinase/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis. J Neurosci, 26(21): 5638-5648
CrossRef Google scholar
[89]
Smith A J, Schlichtenbrede F C, Tschernutter M, Bainbridge J W, Thrasher A J, Ali R R (2003). AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa. Mol Ther, 8(2): 188-195
CrossRef Google scholar
[90]
Songyang Z, Shoelson S E, Chaudhuri M, Gish G, Pawson T, Haser W G, King F, Roberts T, Ratnofsky S, Lechleider R J, (1993). SH2 domains recognize specific phosphopeptide sequences. Cell, 72(5): 767-778
CrossRef Google scholar
[91]
Stitt T N, Conn G, Gore M, Lai C, Bruno J, Radziejewski C, Mattsson K, Fisher J, Gies D R, Jones P F, (1995). The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases. Cell, 80(4): 661-670
CrossRef Google scholar
[92]
Sugo T, Dahlbäck B, Holmgren A, Stenflo J (1986). Calcium binding of bovine protein S. Effect of thrombin cleavage and removal of the gamma-carboxyglutamic acid-containing region. J Biol Chem, 261(11): 5116-5120
[93]
Swanson J A, Johnson M T, Beningo K, Post P, Mooseker M, Araki N (1999). A contractile activity that closes phagosomes in macrophages. J Cell Sci, 112(Pt 3): 307-316
[94]
Taylor P R, Carugati A, Fadok V A, Cook H T, Andrews M, Carroll M C, Savill J S, Henson P M, Botto M, Walport M J (2000). A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J Exp Med, 192(3): 359-366
CrossRef Google scholar
[95]
Thorp E, Cui D, Schrijvers D M, Kuriakose G, Tabas I (2008). Mertk receptor mutation reduces efferocytosis efficiency and promotes apoptotic cell accumulation and plaque necrosis in atherosclerotic lesions of apoe-/- mice. Arterioscler Thromb Vasc Biol, 28(8): 1421-1428
CrossRef Google scholar
[96]
Thorp E, Li Y, Bao L, Yao P M, Kuriakose G, Rong J, Fisher E A, Tabas I (2009). Brief report: increased apoptosis in advanced atherosclerotic lesions of Apoe-/- mice lacking macrophage Bcl-2. Arterioscler Thromb Vasc Biol, 29(2): 169-172
CrossRef Google scholar
[97]
Tibrewal N, Wu Y, D’mello V, Akakura R, George T C, Varnum B, Birge R B (2008). Autophosphorylation docking site Tyr-867 in Mer receptor tyrosine kinase allows for dissociation of multiple signaling pathways for phagocytosis of apoptotic cells and down-modulation of lipopolysaccharide-inducible NF-kappaB transcriptional activation. J Biol Chem, 283(6): 3618-3627
CrossRef Google scholar
[98]
Todt J C, Hu B, Curtis J L (2004). The receptor tyrosine kinase MerTK activates phospholipase C gamma2 during recognition of apoptotic thymocytes by murine macrophages. J Leukoc Biol, 75(4): 705-713
CrossRef Google scholar
[100]
Tschernutter M, Jenkins S A, Waseem N H, Saihan Z, Holder G E, Bird A C, Bhattacharya S S, Ali R R, Webster A R (2006). Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene. Br J Ophthalmol, 90(6): 718-723
CrossRef Google scholar
[99]
Tschernutter M, Schlichtenbrede F C, Howe S, Balaggan K S, Munro P M, Bainbridge J W, Thrasher A J, Smith A J, Ali R R (2005). Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther, 12(8): 694-701
CrossRef Google scholar
[101]
Vollrath D, Feng W, Duncan J L, Yasumura D, D’Cruz P M, Chappelow A, Matthes M T, Kay M A, LaVail M M (2001). Correction of the retinal dystrophy phenotype of the RCS rat by viral gene transfer of Mertk. Proc Natl Acad Sci U S A, 98(22): 12584-12589
CrossRef Google scholar
[102]
Wang H, Wang H, Xiong W, Chen Y, Ma Q, Ma J, Ge Y, Han D (2006). Evaluation on the phagocytosis of apoptotic spermatogenic cells by Sertoli cells in vitro through detecting lipid droplet formation by Oil Red O staining. Reproduction, 132(3): 485-492
CrossRef Google scholar
[103]
Williams J C, Craven R R, Earp H S, Kawula T H, Matsushima G K (2009). TAM receptors are dispensable in the phagocytosis and killing of bacteria. Cell Immunol, 259(2): 128-134
CrossRef Google scholar
[104]
Wu Y, Singh S, Georgescu M M, Birge R B (2005). A role for Mer tyrosine kinase in alphavbeta5 integrin-mediated phagocytosis of apoptotic cells. J Cell Sci, 118(Pt 3): 539-553
CrossRef Google scholar
[105]
Xiong W, Chen Y, Wang H, Wang H, Wu H, Lu Q, Han D (2008). Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells. Reproduction, 135(1): 77-87
CrossRef Google scholar
[106]
Young R W (1967). The renewal of photoreceptor cell outer segments. J Cell Biol, 33(1): 61-72
CrossRef Google scholar
[107]
Young R W, Bok D (1969). Participation of the retinal pigment epithelium in the rod outer segment renewal process. J Cell Biol, 42(2): 392-403
CrossRef Google scholar
[108]
Zheng Y, Zhang L, Lu Q, Wang X, Yu F, Wang X, Lu Q (2009). NGF-induced Tyro3 and Axl function as survival factors for differentiating PC12 cells. Biochem Biophys Res Commun, 378(3): 371-375
CrossRef Google scholar

Acknowledgement

This study was partially supported by NIH EY018830, RR017702, and RR018733 and Research to Prevent Blindness; and the National Natural Science Foundation of China (Grant Nos. 30400229, 30670643 and 30870788).

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
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