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Semin Thromb Hemost 2013; 39(04): 338-346
DOI: 10.1055/s-0033-1334143
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Annexin A2 System in Human Biology: Cell Surface and Beyond

Min Luo
1   Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York
,
Katherine A. Hajjar
1   Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York
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Publikationsdatum:
12. März 2013 (online)

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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]