Annexin A2 System in Human Biology: Cell Surface and Beyond

Abstract

Annexin A2 (A2) is a multicompartmental, multifunctional protein that orchestrates a growing spectrum of biologic processes. At the endothelial cell surface, A2 and S100A10 (p11) form a heterotetramer, which accelerates tissue plasminogen activator–dependent activation of the fibrinolytic protease, plasmin. In antiphospholipid syndrome, anti-A2 antibodies are associated with clinical thrombosis, whereas overexpression of A2 in acute promyelocytic leukemia promotes hyperfibrinolytic bleeding. A2 is upregulated in hypoxia, and mice deficient in A2 are resistant to oxygen-induced retinal neovascularization, suggesting a role for A2 in human retinal vascular proliferation. In solid malignancies, the (A2•p11)₂ tetramer may promote cancer cell invasion, whereas in multiple myeloma A2 enables malignant plasmacyte growth and predicts prognosis. In the central nervous system, the p11 enables membrane insertion of serotonin receptors that govern mood. In the peripheral nervous system, p11 directs sodium channels to the plasma membrane, enabling pain perception. In cerebral cortex neurons, A2 stabilizes the microtubule-associated tau protein, which, when mutated, is associated with frontotemporal dementia. In inflammatory dendritic cells, A2 maintains late endosomal/lysosomal membrane integrity, thus modulating inflammasome activation and cytokine secretion in a model of aseptic arthritis. Together, these findings suggest an emerging, multifaceted role for A2 in human health and disease.

Keywords

annexin A2 - S100A2/protein p11 - fibrinolysis - inflammation

Note

We note that use of the term annexin A2 “tetramer,” which consists of both annexin A2 and p11 subunits, and nomination of p11 as a potential plasminogen binding site have been discussed in two previously published studies.[128] [129]

• References

• 1 Moss SE, Morgan RO. The annexins. Genome Biol 2004; 5: 1-8
• 2 Rand JH. “Annexinopathies”—a new class of diseases. N Engl J Med 1999; 340 (13) 1035-1036
• 3 Rand JH. The annexinopathies: a new category of diseases. Biochim Biophys Acta 2000; 1498 (2-3) 169-173
• 4 Hayes MJ, Moss SE. Annexins and disease. Biochem Biophys Res Commun 2004; 322 (4) 1166-1170
• 5 Hayes MJ, Longbottom RE, Evans MA, Moss SE. Annexinopathies. Subcell Biochem 2007; 45: 1-28
• 6 Fatimathas L, Moss SE. Annexins as disease modifiers. Histol Histopathol 2010; 25 (4) 527-532
• 7 Heizmann CW, Ackermann GE, Galichet A. Pathologies involving the S100 proteins and RAGE. Subcell Biochem 2007; 45: 93-138
• 8 Hedhli N, Falcone DJ, Huang B , et al. The annexin A2/S100A10 system in health and disease: emerging paradigms. J Biomed Biotechnol 2012; 2012: 406273
• 9 Gerke V, Creutz CE, Moss SE. Annexins: linking Ca2+ signalling to membrane dynamics. Nat Rev Mol Cell Biol 2005; 6 (6) 449-461
• 10 Gerke V, Moss SE. Annexins: from structure to function. Physiol Rev 2002; 82 (2) 331-371
• 11 Spano F, Raugei G, Palla E, Colella C, Melli M. Characterization of the human lipocortin-2-encoding multigene family: its structure suggests the existence of a short amino acid unit undergoing duplication. Gene 1990; 95 (2) 243-251
• 12 Waisman DM. Annexin II tetramer: structure and function. Mol Cell Biochem 1995; 149-150: 301-322
• 13 Rescher U, Gerke V. S100A10/p11: Family, friends, and functions. . Pflugers Arch Eur J Physiol 2007; 455: 575-582
• 14 Donato R. S100: a multigenic family of calcium-modulated proteins of the EF-hand type with intracellular and extracellular functional roles. Int J Biochem Cell Biol 2001; 33 (7) 637-668
• 15 Réty S, Sopkova J, Renouard M , et al. The crystal structure of a complex of p11 with the annexin II N-terminal peptide. Nat Struct Biol 1999; 6 (1) 89-95
• 16 Knop M, Aareskjold E, Bode G, Gerke V. Rab3D and annexin A2 play a role in regulated secretion of vWF, but not tPA, from endothelial cells. EMBO J 2004; 23 (15) 2982-2992
• 17 Umbrecht-Jenck E, Demais V, Calco V, Bailly Y, Bader MF, Chasserot-Golaz S. S100A10-mediated translocation of annexin-A2 to SNARE proteins in adrenergic chromaffin cells undergoing exocytosis. Traffic 2010; 11 (7) 958-971
• 18 Wang P, Chintagari NR, Gou D, Su L, Liu L. Physical and functional interactions of SNAP-23 with annexin A2. Am J Respir Cell Mol Biol 2007; 37 (4) 467-476
• 19 Zobiack N, Rescher U, Ludwig C, Zeuschner D, Gerke V. The annexin 2/S100A10 complex controls the distribution of transferrin receptor-containing recycling endosomes. Mol Biol Cell 2003; 14 (12) 4896-4908
• 20 Eberhard DA, Karns LR, VandenBerg SR, Creutz CE. Control of the nuclear-cytoplasmic partitioning of annexin II by a nuclear export signal and by p11 binding. J Cell Sci 2001; 114 (Pt 17) 3155-3166
• 21 Vedeler A, Hollås H, Grindheim AK, Raddum AM. Multiple roles of annexin A2 in post-transcriptional regulation of gene expression. Curr Protein Pept Sci 2012; 13 (4) 401-412
• 22 Grieve AG, Moss SE, Hayes MJ. Annexin A2 at the interface of actin and membrane dynamics: a focus on its roles in endocytosis and cell polarization. Int J Cell Biol 2012; 2012: 852430
• 23 Flood EC, Hajjar KA. The annexin A2 system and vascular homeostasis. Vascul Pharmacol 2011; 54 (3-6) 59-67
• 24 Dassah M, Deora AB, He K, Hajjar KA. The endothelial cell annexin A2 system and vascular fibrinolysis. Gen Physiol Biophys 2009; 28 Spec No Focus: F20-F28
• 25 Madureira PA, Surette AP, Phipps KD, Taboski MAS, Miller VA, Waisman DM. The role of the annexin A2 heterotetramer in vascular fibrinolysis. Blood 2011; 118 (18) 4789-4797
• 26 Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol 2005; 129 (3) 307-321
• 27 Hajjar KA. The molecular basis of fibrinolysis. In: Orkin SH, Nathan DG, Ginsburg D, Look AT, Fisher DE, Lux SE, , eds. Nathan and Oski's Hematology of Infancy and Childhood. 7th ed. Philadelphia: Saunders Elsevier; 2009: 1425-1447
• 28 Hajjar KA, Ruan J. Fibrinolysis and thrombolysis. In: Kaushansky K, Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Prchal JT, , eds. Williams Hematology. 8th ed. New York: McGraw-Hill; 2010: 2219-2246
• 29 Valapala M, Vishwanatha JK. Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2. J Biol Chem 2011; 286 (35) 30911-30925
• 30 Faure AV, Migné C, Devilliers G, Ayala-Sanmartin J. Annexin 2 “secretion” accompanying exocytosis of chromaffin cells: possible mechanisms of annexin release. Exp Cell Res 2002; 276 (1) 79-89
• 31 Danielsen EM, van Deurs B, Hansen GH. “Nonclassical” secretion of annexin A2 to the lumenal side of the enterocyte brush border membrane. Biochemistry 2003; 42 (49) 14670-14676
• 32 Keller M, Rüegg A, Werner S, Beer HD. Active caspase-1 is a regulator of unconventional protein secretion. Cell 2008; 132 (5) 818-831
• 33 Peterson EA, Sutherland MR, Nesheim ME, Pryzdial EL. Thrombin induces endothelial cell-surface exposure of the plasminogen receptor annexin 2. J Cell Sci 2003; 116 (Pt 12) 2399-2408
• 34 Deora AB, Kreitzer G, Jacovina AT, Hajjar KA. An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface. J Biol Chem 2004; 279 (42) 43411-43418
• 35 Huang B, Deora AB, He KL , et al. Hypoxia-inducible factor-1 drives annexin A2 system-mediated perivascular fibrin clearance in oxygen-induced retinopathy in mice. Blood 2011; 118 (10) 2918-2929
• 36 Erikson E, Erikson RL. Identification of a cellular protein substrate phosphorylated by the avian sarcoma virus-transforming gene product. Cell 1980; 21 (3) 829-836
• 37 He KL, Deora AB, Xiong H , et al. Endothelial cell annexin A2 regulates polyubiquitination and degradation of its binding partner S100A10/p11. J Biol Chem 2008; 283 (28) 19192-19200
• 38 He KL, Sui G, Xiong H , et al. Feedback regulation of endothelial cell surface plasmin generation by PKC-dependent phosphorylation of annexin A2. J Biol Chem 2011; 286 (17) 15428-15439
• 39 Jost M, Gerke V. Mapping of a regulatory important site for protein kinase C phosphorylation in the N-terminal domain of annexin II. Biochim Biophys Acta 1996; 1313 (3) 283-289
• 40 Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J Biol Chem 1994; 269 (33) 21191-21197
• 41 Cesarman GM, Guevara CA, Hajjar KA. An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem 1994; 269 (33) 21198-21203
• 42 O'Connell PA, Surette AP, Liwski RS, Svenningsson P, Waisman DM. S100A10 regulates plasminogen-dependent macrophage invasion. Blood 2010; 116 (7) 1136-1146
• 43 Das R, Burke T, Plow EF. Histone H2B as a functionally important plasminogen receptor on macrophages. Blood 2007; 110 (10) 3763-3772
• 44 Hajjar KA, Mauri L, Jacovina AT , et al. Tissue plasminogen activator binding to the annexin II tail domain. Direct modulation by homocysteine. J Biol Chem 1998; 273 (16) 9987-9993
• 45 Hajjar KA, Guevara CA, Lev E, Dowling K, Chacko J. Interaction of the fibrinolytic receptor, annexin II, with the endothelial cell surface. Essential role of endonexin repeat 2. J Biol Chem 1996; 271 (35) 21652-21659
• 46 Ling Q, Jacovina AT, Deora AB , et al. Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo. J Clin Invest 2004; 113 (1) 38-48
• 47 Surette AP, Madureira PA, Phipps KD, Miller VA, Svenningsson P, Waisman DM. Regulation of fibrinolysis by S100A10 in vivo. Blood 2011; 118 (11) 3172-3181
• 48 Jacovina AT, Deora AB, Ling Q , et al. Homocysteine inhibits neoangiogenesis in mice through blockade of annexin A2-dependent fibrinolysis. J Clin Invest 2009; 119 (11) 3384-3394
• 49 Selhub J. Homocysteine metabolism. Annu Rev Nutr 1999; 19: 217-246
• 50 Humphrey LL, Fu R, Rogers K, Freeman M, Helfand M. Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis. Mayo Clin Proc 2008; 83 (11) 1203-1212
• 51 Bønaa KH, Njølstad I, Ueland PM , et al; NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354 (15) 1578-1588
• 52 Hajjar KA. Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J Clin Invest 1993; 91 (6) 2873-2879
• 53 Markus HS. Genes, endothelial function and cerebral small vessel disease in man. Exp Physiol 2008; 93 (1) 121-127
• 54 Wong A, Mok V, Fan YH, Lam WWM, Liang KS, Wong KS. Hyperhomocysteinemia is associated with volumetric white matter change in patients with small vessel disease. J Neurol 2006; 253 (4) 441-447
• 55 Zhu H, Fan X, Yu Z , et al. Annexin A2 combined with low-dose tPA improves thrombolytic therapy in a rat model of focal embolic stroke. J Cereb Blood Flow Metab 2010; 30 (6) 1137-1146
• 56 Tanaka Y, Ishii H, Hiraoka M , et al. Efficacy of recombinant annexin 2 for fibrinolytic therapy in a rat embolic stroke model: a magnetic resonance imaging study. Brain Res 2007; 1165: 135-143
• 57 Walvick RP, Bråtane BT, Henninger N , et al. Visualization of clot lysis in a rat embolic stroke model: application to comparative lytic efficacy. Stroke 2011; 42 (4) 1110-1115
• 58 Ishii H, Yoshida M, Hiraoka M , et al. Recombinant annexin II modulates impaired fibrinolytic activity in vitro and in rat carotid artery. Circ Res 2001; 89 (12) 1240-1245
• 59 Fan X, Yu Z, Liu J , et al. Annexin A2: a tissue plasminogen activator amplifier for thrombolytic stroke therapy. Stroke 2010; 41 (10, Suppl) S54-S58
• 60 Yepes M, Sandkvist M, Moore EG, Bugge TH, Strickland DK, Lawrence DA. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest 2003; 112 (10) 1533-1540
• 61 Wang X, Tsuji K, Lee SR , et al. Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke. Stroke 2004; 35 (11) (Suppl. 01) 2726-2730
• 62 Kaur J, Zhao Z, Klein GM, Lo EH, Buchan AM. The neurotoxicity of tissue plasminogen activator?. J Cereb Blood Flow Metab 2004; 24 (9) 945-963
• 63 Cockrell E, Espinola RG, McCrae KR. Annexin A2: biology and relevance to the antiphospholipid syndrome. Lupus 2008; 17 (10) 943-951
• 64 Cohen D, Berger SP, Steup-Beekman GM, Bloemenkamp KWM, Bajema IM. Diagnosis and management of the antiphosphlipid syndrome. BMJ 2010; 340: 1125-1132
• 65 Cesarman-Maus G, Ríos-Luna NP, Deora AB , et al. Autoantibodies against the fibrinolytic receptor, annexin 2, in antiphospholipid syndrome. Blood 2006; 107 (11) 4375-4382
• 66 Ao W, Zheng H, Chen XW, Shen Y, Yang CD. Anti-annexin II antibody is associated with thrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis. Rheumatol Int 2011; 31 (7) 865-869
• 67 Cesarman-Maus G, Cantú-Brito C, Barinagarrementeria F , et al. Autoantibodies against the fibrinolytic receptor, annexin A2, in cerebral venous thrombosis. Stroke 2011; 42 (2) 501-503
• 68 Salle V, Mazière JC, Brulé A , et al. Antibodies against the N-terminal domain of annexin A2 in antiphospholipid syndrome. Eur J Intern Med 2012; 23 (7) 665-668
• 69 Salle V, Mazière JC, Smail A , et al. Anti-annexin II antibodies in systemic autoimmune diseases and antiphospholipid syndrome. J Clin Immunol 2008; 28 (4) 291-297
• 70 Ao W, Zheng H, Chen XW, Shen Y, Yang CD. Anti-annexin II antibody is associated with thrombosis and/or pregnancy morbidity in antiphospholipid syndrome and systemic lupus erythematosus with thrombosis. Rheumatol Int 2011; 31 (7) 865-869
• 71 Yung S, Cheung KF, Zhang QY, Chan TM. Anti-dsDNA antibodies bind to mesangial annexin II in lupus nephritis. J Am Soc Nephrol 2010; 21 (11) 1912-1927
• 72 Krone KA, Allen KL, McCrae KR. Impaired fibrinolysis in the antiphospholipid syndrome. Curr Rheumatol Rep 2010; 12 (1) 53-57
• 73 Platt OS. Preventing stroke in sickle cell anemia. N Engl J Med 2005; 353 (26) 2743-2745
• 74 Sebastiani P, Ramoni MF, Nolan V, Baldwin CT, Steinberg MH. Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet 2005; 37 (4) 435-440
• 75 Flanagan JM, Frohlich DM, Howard TA , et al. Genetic predictors for stroke in children with sickle cell anemia. Blood 2011; 117 (24) 6681-6684
• 76 Baldwin CT, Nolan VG, Wyszynski DF , et al. Association of klotho, bone morphogenic protein 6, and annexin A2 polymorphisms with sickle cell osteonecrosis. Blood 2005; 106 (1) 372-375
• 77 Ashley-Koch AE, Elliott L, Kail ME , et al. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood 2008; 111 (12) 5721-5726
• 78 Stein E, McMahon B, Kwaan H, Altman JK, Frankfurt O, Tallman MS. The coagulopathy of acute promyelocytic leukaemia revisited. Best Pract Res Clin Haematol 2009; 22 (1) 153-163
• 79 Menell JS, Cesarman GM, Jacovina AT, McLaughlin MA, Lev EA, Hajjar KA. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med 1999; 340 (13) 994-1004
• 80 Liu Y, Wang Z, Jiang M , et al. The expression of annexin II and its role in the fibrinolytic activity in acute promyelocytic leukemia. Leuk Res 2011; 35 (7) 879-884
• 81 O'Connell PA, Madureira PA, Berman JN, Liwski RS, Waisman DM. Regulation of S100A10 by the PML-RAR-α oncoprotein. Blood 2011; 117 (15) 4095-4105
• 82 Jácomo RH, Santana-Lemos BA, Lima ASG , et al. Methionine-induced hyperhomocysteinemia reverts fibrinolytic pathway activation in a murine model of acute promyelocytic leukemia. Blood 2012; 120 (1) 207-213
• 83 Smith LE, Wesolowski E, McLellan A , et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 1994; 35 (1) 101-111
• 84 Valapala M, Thamake SI, Vishwanatha JK. A competitive hexapeptide inhibitor of annexin A2 prevents hypoxia-induced angiogenic events. J Cell Sci 2011; 124 (Pt 9) 1453-1464
• 85 Zhao S, Huang L, Wu J, Zhang Y, Pan D, Liu X. Vascular endothelial growth factor upregulates expression of annexin A2 in vitro and in a mouse model of ischemic retinopathy. Mol Vis 2009; 15: 1231-1242
• 86 Sato T, Kusaka S, Hashida N, Saishin Y, Fujikado T, Tano Y. Comprehensive gene-expression profile in murine oxygen-induced retinopathy. Br J Ophthalmol 2009; 93 (1) 96-103
• 87 Zhao SH, Pan DY, Zhang Y, Wu JH, Liu X, Xu Y. Annexin A2 promotes choroidal neovascularization by increasing vascular endothelial growth factor expression in a rat model of argon laser coagulation-induced choroidal neovascularization. Chin Med J (Engl) 2010; 123 (6) 713-721
• 88 Lima e Silva R, Shen J, Gong YY , et al. Agents that bind annexin A2 suppress ocular neovascularization. J Cell Physiol 2010; 225 (3) 855-864
• 89 Rao JS. Molecular mechanisms of glioma invasiveness: the role of proteases. Nat Rev Cancer 2003; 3 (7) 489-501
• 90 Tsatas D, Kaye AH. The role of the plasminogen activation cascade in glioma cell invasion: a review. J Clin Neurosci 2003; 10 (2) 139-145
• 91 Maruo T, Ichikawa T, Kanzaki H , et al. Proteomics-based analysis of invasion-related proteins in malignant gliomas. Neuropathology 2012; ; Epub ahead of print
• 92 Beckner ME, Chen X, An J, Day BW, Pollack IF. Proteomic characterization of harvested pseudopodia with differential gel electrophoresis and specific antibodies. Lab Invest 2005; 85 (3) 316-327
• 93 Zhai H, Acharya S, Gravanis I , et al. Annexin A2 promotes tumor progression in glioma cells. J Neurosci 2011; 31 (40) 14346-14360
• 94 Reeves SA, Chavez-Kappel C, Davis R, Rosenblum M, Israel MA. Developmental regulation of annexin II (lipocortin 2) in human brain and expression in high grade glioma. Cancer Res 1992; 52 (24) 6871-6876
• 95 Nygaard SJ, Haugland HK, Kristoffersen EK, Lund-Johansen M, Laerum OD, Tysnes OB. Expression of annexin II in glioma cell lines and in brain tumor biopsies. J Neurooncol 1998; 38 (1) 11-18
• 96 Roseman BJ, Bollen A, Hsu J, Lamborn K, Israel MA. Annexin II marks astrocytic brain tumors of high histologic grade. Oncol Res 1994; 6 (12) 561-567
• 97 Sharma M, Blackman MR, Sharma MC. Antibody-directed neutralization of annexin II (ANX II) inhibits neoangiogenesis and human breast tumor growth in a xenograft model. Exp Mol Pathol 2012; 92 (1) 175-184
• 98 Sharma MR, Koltowski L, Ownbey RT, Tuszynski GP, Sharma MC. Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 2006; 81 (2) 146-156
• 99 Sharma M, Ownbey RT, Sharma MC. Breast cancer cell surface annexin II induces cell migration and neoangiogenesis via tPA dependent plasmin generation. Exp Mol Pathol 2010; 88 (2) 278-286
• 100 Phipps KD, Surette AP, O'Connell PA, Waisman DM. Plasmingen receptor S100A10 is essential for the migration of tumor-promoting macrophages into tumor sites. Cancer Res 2011; 7: 6676-6683
• 101 Swisher JFA, Burton N, Bacot SM, Vogel SN, Feldman GM. Annexin A2 tetramer activates human and murine macrophages through TLR4. Blood 2010; 115 (3) 549-558
• 102 Seckinger A, Meissner T, Moreaux J , et al. Clinical and prognostic role of annexin A2 in multiple myleoma. Blood 2012; 120: 10871094
• 103 Claudio JO, Masih-Khan E, Tang H , et al. A molecular compendium of genes expressed in multiple myeloma. Blood 2002; 100 (6) 2175-2186
• 104 Bao H, Jiang M, Zhu M, Sheng F, Ruan J, Ruan C. Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol 2009; 90 (2) 177-185
• 105 D'Souza S, Kurihara N, Shiozawa Y , et al. Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment. Blood 2012; 119 (8) 1888-1896
• 106 Shiozawa Y, Havens AM, Jung Y , et al. Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 2008; 105 (2) 370-380
• 107 Svenningsson P, Greengard P. p11 (S100A10)—an inducible adaptor protein that modulates neuronal functions. Curr Opin Pharmacol 2007; 7 (1) 27-32
• 108 Svenningsson P, Chergui K, Rachleff I , et al. Alterations in 5-HT1B receptor function by p11 in depression-like states. Science 2006; 311 (5757) 77-80
• 109 Alexander B, Warner-Schmidt JL, Eriksson T , et al. Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens. Sci Transl Med 2010; 2 (54) 54ra76
• 110 Zhang L, Su TP, Choi K , et al. P11 (S100A10) as a potential biomarker of psychiatric patients at risk of suicide. J Psychiatr Res 2011; 45 (4) 435-441
• 111 Huang XL, Pawliczak R, Yao XL , et al. Interferon-gamma induces p11 gene and protein expression in human epithelial cells through interferon-gamma-activated sequences in the p11 promoter. J Biol Chem 2003; 278 (11) 9298-9308
• 112 Warner-Schmidt JL, Vanover KE, Chen EY, Marshall JJ, Greengard P. Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci USA 2011; 108 (22) 9262-9267
• 113 Chen G, Twyman R, Manji HK. p11 and gene therapy for severe psychiatric disorders: a practical goal?. Sci Transl Med 2010; 2 (54) 54ps51
• 114 Okuse K, Malik-Hall M, Baker MD , et al. Annexin II light chain regulates sensory neuron-specific sodium channel expression. Nature 2002; 417 (6889) 653-656
• 115 Rezvanpour A, Shaw GS. Unique S100 target protein interactions. Gen Physiol Biophys 2009; 28 Spec No Focus: F39-F46
• 116 Foulkes T, Nassar MA, Lane T , et al. Deletion of annexin 2 light chain p11 in nociceptors causes deficits in somatosensory coding and pain behavior. J Neurosci 2006; 26 (41) 10499-10507
• 117 Mishra M, Paunesku T, Woloschak GE , et al. Gene expression analysis of frontotemporal lobar degeneration of the motor neuron disease type with ubiquitinated inclusions. Acta Neuropathol 2007; 114 (1) 81-94
• 118 Paulson HL, Igo I. Genetics of dementia. Semin Neurol 2011; 31 (5) 449-460
• 119 Gauthier-Kemper A, Weissmann C, Golovyashkina N , et al. The frontotemporal dementia mutation R406W blocks tau's interaction with the membrane in an annexin A2-dependent manner. J Cell Biol 2011; 192 (4) 647-661
• 120 Bashir R, Britton S, Strachan T , et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat Genet 1998; 20 (1) 37-42
• 121 Liu J, Aoki M, Illa I , et al. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet 1998; 20 (1) 31-36
• 122 Campanaro S, Romualdi C, Fanin M , et al. Gene expression profiling in dysferlinopathies using a dedicated muscle microarray. Hum Mol Genet 2002; 11 (26) 3283-3298
• 123 Cagliani R, Magri F, Toscano A , et al. Mutation finding in patients with dysferlin deficiency and role of the dysferlin interacting proteins annexin A1 and A2 in muscular dystrophies. Hum Mutat 2005; 26 (3) 283
• 124 Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown Jr RH. Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing. J Biol Chem 2003; 278 (50) 50466-50473
• 125 Cobelli N, Scharf B, Crisi GM, Hardin J, Santambrogio L. Mediators of the inflammatory response to joint replacement devices. Nat Rev Rheumatol 2011; 7 (10) 600-608
• 126 Maitra R, Clement CC, Scharf B , et al. Endosomal damage and TLR2 mediated inflammasome activation by alkane particles in the generation of aseptic osteolysis. Mol Immunol 2009; 47 (2-3) 175-184
• 127 Scharf B, Clement CC, Wu XX , et al. Annexin A2 binds to endosomes following organelle destabilization by particulate wear debris. Nat Commun 2012; 3: 755-765
• 128 Kassam G, Choi KS, Ghuman J , et al. The role of annexin II tetramer in the activation of plasminogen. J Biol Chem 1998; 273 (8) 4790-4799
• 129 Kassam G, Le BH, Choi KS , et al. The p11 subunit of the annexin II tetramer plays a key role in the stimulation of t-PA-dependent plasminogen activation. Biochemistry 1998; 37: 16958-16966