Regulation of actin dynamics by annexin 2

Hayes, Matthew J.; Shao, Dongmin; Bailly, Maryse; Moss, Stephen E.

doi:10.1038/sj.emboj.7601078

Cited by 179 publications

(186 citation statements)

References 45 publications

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“…A2IC plays an important role in the function of annexin A2 and contains an intracellular binding site for Ca 2+ , phospholipids and F-actin [12,20] . In the present work, we also found that the interaction between A2IC and actin is essential for maintaining the plasticity of the dynamic membrane-associated actin cytoskeleton [21] . The interaction of A2IC with other proteins could play a critical role in plasmindependent cell activation.…”

Section: Discussionsupporting

confidence: 75%

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2

Laumonnier

Syrovets

et al. 2011

Acta Pharmacol Sin

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Aim: To identify proteins that interact with the C-terminal fragment of annexin A2 (A2IC), generated by plasmin cleavage of the plasmin receptor, a heterotetramer (AA2t) containing annexin A2. Methods: The gene that encodes the A2IC fragment was obtained from PCR-amplified cDNA isolated from human monocytes, and was ligated into the pBTM116 vector using a DNA ligation kit. The resultant plasmid (pBTM116-A2IC) was sequenced with an ABI PRISM 310 Genetic Analyzer. The expression of an A2IC bait protein fused with a LexA-DNA binding domain (BD) was determined using Western blot analysis. The identification of proteins that interact with A2IC and are encoded in a human monocyte cDNA library was performed using yeast two-hybrid screening. The DNA sequences of the relevant cDNAs were determined using an ABI PRISM BigDye terminator cycle sequencing ready reaction kit. Nucleotide sequence databases were searched for homologous sequences using BLAST search analysis (http://www.ncbi.nlm.nih.gov). Confirmation of the interaction between the protein LexA-A2IC and each of cathepsin S and SNX17 was conducted using a small-scale yeast transformation and X-gal assay. Results: The yeast transformed with plasmids encoding the bait proteins were screened with a human monocyte cDNA library by reconstituting full-length transcription factors containing the GAL4-active domain (GAL4-AD) as the prey in a yeast two-hybrid approach. After screening 1×10 7 clones, 23 independent β-Gal-positive clones were identified. Sequence analysis and a database search revealed that 15 of these positive clones matched eight different proteins (SNX17, ProCathepsin S, RPS2, ZBTB4, OGDH, CCDC32, PAPD4, and actin which was already known to interact with annexin A2). Conclusion: A2IC A2IC interacts with various proteins to form protein complexes, which may contribute to the molecular mechanism of monocyte activation induced by plasmin. The yeast two-hybrid system is an efficient approach for investigating protein interactions.Keywords: yeast yeast two-hybrid system; human monocyte; plasmin receptor; C-terminal fragment of annexin A2 (A2IC); protein-protein interaction Acta

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Section: Discussionsupporting

confidence: 75%

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2

Laumonnier

Syrovets

et al. 2011

Acta Pharmacol Sin

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“…For these experiments, confluent cultures were maintained at high density for 2 wk on glass coverslips before exposure to fluorescently labeled POS and subsequent fixation at defined time points. Cells were immunostained for anx A2 and also F-actin, because reorganization of the actin cytoskeleton is a key early event in phagocytosis, and in previous work we have shown that anx A2 is an important regulator of actin dynamics (Hayes et al, 2006). Confocal microscopy revealed enrichment of anx A2 and F-actin at the point of contact between POS aggregates and the apical RPE cell surface (arrowhead in Figure 2A).…”

Section: Anx A2 Is Recruited To the Forming Phagosomementioning

confidence: 78%

“…It has been proposed that phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P 2 ) at the site of formation of the phagocytic cup and its subsequent hydrolysis as the cup closes are the key signaling events regulating the cycle of actin polymerization and depolymerization (Botelho et al, 2000;Scott et al, 2005). Because anx A2 is a potent regulator of actin dynamics (Merrifield et al, 2001;Hayes et al, 2006) and binds both cholesterol-rich membranes, Ca 2ϩ , and PtdIns4,5P 2 Rescher et al, 2004;Gerke et al, 2005), it is well placed to function as a sensor of these second messengers and signaling intermediates, linking . Tyrosine kinase signaling is defective in anx A2-deficient retinas.…”

Section: Discussionmentioning

confidence: 99%

Annexin A2 Regulates Phagocytosis of Photoreceptor Outer Segments in the Mouse Retina

Law

Hajjar

et al. 2009

MBoC

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The daily phagocytosis of shed photoreceptor outer segments by pigment epithelial cells is critical for the maintenance of the retina. In a subtractive polymerase chain reaction analysis, we found that functional differentiation of human ARPE19 retinal pigment epithelial (RPE) cells is accompanied by up-regulation of annexin (anx) A2, a major Src substrate and regulator of membrane-cytoskeleton dynamics. Here, we show that anx A2 is recruited to the nascent phagocytic cup in vitro and in vivo and that it fully dissociates once the phagosome is internalized. In ARPE19 cells depleted of anx A2 by using small interfering RNA and in ANX A2 ؊/؊ mice the phagocytosis of outer segments was impaired, and in ANX A2 ؊/؊ mice there was an accumulation of phagocytosed outer segments in the RPE apical processes, indicative of retarded phagosome transport. We show that anx A2 is tyrosine phosphorylated at the onset of phagocytosis and that the synchronized activation of focal adhesion kinase and c-Src is abnormal in ANX A2 ؊/؊ mice. These findings reveal that anx A2 is involved in the circadian regulation of outer segment phagocytosis, and they provide new insight into the protein machinery that regulates phagocytic function in RPE cells. INTRODUCTIONThe retinal pigment epithelium (RPE) performs a range of functions that directly support the retina (Strauss, 2005), including the daily phagocytosis and digestion of shed photoreceptor outer segments (POS). The importance of this activity is exemplified in the dystrophic Royal College of Surgeons rat, which due to a failure in phagocytosis undergoes a progressive and rapid retinal degeneration characterized by accumulation of cellular debris and photoreceptor cell death. The gene responsible for this pathology was identified by positional cloning as the Mer tyrosine kinase (MerTK), a key signaling intermediate that is expressed in RPE cells and plays an essential role in the internalization of bound POS (Chaitin and Hall, 1983;D'Cruz et al., 2000). Recent studies have provided insight into other RPE cell proteins that have distinct roles either in the binding or the internalization of shed POS. For example, the apically expressed ␣v␤5 integrin is required for efficient binding of POS, and RPE cells from ␤5 Ϫ/Ϫ mice show markedly reduced binding of POS in vitro (Nandrot et al., 2004). Intriguingly, engagement of the ␣v␤5 integrin by its cognate ligand, milk fat globule-EGF8 (MFG-E8), is essential for the circadian synchronization of phagocytosis (Nandrot and Finnemann, 2006;Nandrot et al., 2007), and although phagocytosis of POS occurs in MFG-E8 Ϫ/Ϫ and ␤5 Ϫ/Ϫ mice, in both mutants the daily rhythm is absent. In contrast, focal adhesion kinase (FAK) and MerTK are not required for the initial binding of POS to the apical surface of the RPE, but they are sequentially activated by ␣v␤5 receptors and are essential for phagosome internalization (Feng et al., 2002;Finnemann, 2003).Between the pigment epithelium and neuroretina RPE cells extend apical processes into the interphotorecept...

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“…Interestingly, annexin A2 appears to be a necessary component of the machinery controlling endosomal membrane dynamics and multivesicular endosome biogenesis, and, in particular the clathrin-dependent endocytosis [71]. Annexin A2 also participates in the regulation of actin dynamics which is an important step in the endocytosis machinery [72]. ApoER2' may also facilitate endocytosis and signal transduction [73].…”

Section: Internalization and Apla Receptorsmentioning

confidence: 99%

Receptors involved in cell activation by antiphospholipid antibodies

Brandt

Kruithof

Moerloose

2013

Thrombosis Research

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The antiphospholipid syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). The plasma protein β2-glycoprotein 1 (β2GP1) has been identified as a major target of aPLA associated with APS. Cell activation by aPLA appears to be a major pathogenic cause in the pathogenesis of APS. Receptors, co-receptors and accessory molecules are known to assist the pathogenic effects of aPLA. Members of the TLR family and the platelet receptor apolipoprotein E receptor 2' (apoER2'), a receptor belonging to the low-density lipoprotein receptor (LDL-R) family, as well as GPIbα, were identified as putative candidates for aPLA recognition. CD14, a co-receptor for TLR2 and TLR4, and annexin A2, a ubiquitous Ca2+ -binding protein that is essential for actin-dependent vesicle transport, could serve as important accessory molecules in mediating the pathogenic effects of aPLA. Finally, complement activation has been reported in association with the pathogenicity of APS. The relative contribution of these different mechanisms in the pathogenesis of APS is controversial. Here, we review the various in vivo and in vitro models that have been used to investigate the pathogenic mechanisms of aPLA in APS

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Regulation of actin dynamics by annexin 2

Cited by 179 publications

References 45 publications

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2

Yeast two-hybrid screening of proteins interacting with plasmin receptor subunit: C-terminal fragment of annexin A2

Annexin A2 Regulates Phagocytosis of Photoreceptor Outer Segments in the Mouse Retina

Receptors involved in cell activation by antiphospholipid antibodies

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