scholarly journals The Annexin A2/S100A10 Complex: The Mutualistic Symbiosis of Two Distinct Proteins

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1849
Author(s):  
Alamelu Bharadwaj ◽  
Emma Kempster ◽  
David Morton Waisman
Keyword(s):  
Plasma Membrane ◽  
Annexin A2 ◽  
Neurotransmitter Receptors ◽  
Symbiotic Relationship ◽  
Plasminogen Activation ◽  
S100 Family ◽  
Mutualistic Symbiosis ◽  
Tissue Plasminogen ◽  
The Relationship ◽  
Dependent Processes

Mutualistic symbiosis refers to the symbiotic relationship between individuals of different species in which both individuals benefit from the association. S100A10, a member of the S100 family of Ca2+-binding proteins, exists as a tight dimer and binds two annexin A2 molecules. This association forms the annexin A2/S100A10 complex known as AIIt, and modifies the distinct functions of both proteins. Annexin A2 is a Ca2+-binding protein that binds F-actin, phospholipid, RNA, and specific polysaccharides such as heparin. S100A10 does not bind Ca2+, but binds tPA, plasminogen, certain plasma membrane ion channels, neurotransmitter receptors, and the structural scaffold protein, AHNAK. S100A10 relies on annexin A2 for its intracellular survival: in the absence of annexin A2, it is rapidly destroyed by ubiquitin-dependent and independent proteasomal degradation. Annexin A2 requires S100A10 to increase its affinity for Ca2+, facilitating its participation in Ca2+-dependent processes such as membrane binding. S100A10 binds tissue plasminogen activator and plasminogen, and promotes plasminogen activation to plasmin, which is a process stimulated by annexin A2. In contrast, annexin A2 acts as a plasmin reductase and facilitates the autoproteolytic destruction of plasmin. This review examines the relationship between annexin A2 and S100A10, and how their mutualistic symbiosis affects the function of both proteins.

scholarly journals Annexin A2 Egress during Calcium-Regulated Exocytosis in Neuroendocrine Cells

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2059 ◽  
Author(s):  
Marion Gabel ◽  
Cathy Royer ◽  
Tamou Thahouly ◽  
Valérie Calco ◽  
Stéphane Gasman ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Chromaffin Cells ◽  
Spatial Organization ◽  
Lipid Binding ◽  
Annexin A2 ◽  
Neuroendocrine Cells ◽  
Outer Face ◽  
Tissue Plasminogen

Annexin A2 (AnxA2) is a calcium- and lipid-binding protein involved in neuroendocrine secretion where it participates in the formation and/or stabilization of lipid micro-domains required for structural and spatial organization of the exocytotic machinery. We have recently described that phosphorylation of AnxA2 on Tyr23 is critical for exocytosis. Considering that Tyr23 phosphorylation is known to promote AnxA2 externalization to the outer face of the plasma membrane in different cell types, we examined whether this phenomenon occurred in neurosecretory chromaffin cells. Using immunolabeling and biochemical approaches, we observed that nicotine stimulation triggered the egress of AnxA2 to the external leaflets of the plasma membrane in the vicinity of exocytotic sites. AnxA2 was found co-localized with tissue plasminogen activator, previously described on the surface of chromaffin cells following secretory granule release. We propose that AnxA2 might be a cell surface tissue plasminogen activator receptor for chromaffin cells, thus playing a role in autocrine or paracrine regulation of exocytosis.

scholarly journals Phospholipid flipping facilitates annexin translocation across membranes

2018 ◽  
Author(s):  
Sarah E Stewart ◽  
Avraham Ashkenazi ◽  
Athena Williamson ◽  
David C Rubinsztein ◽  
Kevin Moreau
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Cell Surface ◽  
Binding Proteins ◽  
Annexin A2 ◽  
Plasminogen Activation ◽  
Anoctamin 6 ◽  
Outer Leaflet ◽  
Membrane Cell ◽  
Plasma Membrane Phospholipid

AbstractAnnexins are phospholipid binding proteins that somehow translocate from the inner leaflet of the plasma membrane to the outer leaflet. For example, Annexin A2 is known to localise to the outer leaflet of the plasma membrane (cell surface) where it is involved in plasminogen activation leading to fibrinolysis and cell migration, among other functions. Despite having well described extracellular functions, the mechanism of annexin transport from the cytoplasmic inner leaflet to the extracellular outer leaflet of the plasma membrane remains unclear. Here, we show that phospholipid flipping activity is crucial for the transport of annexins A2 and A5 across membranes in cells and in liposomes. We identified TMEM16F (anoctamin-6) as a lipid scramblase required for transport of these annexins to the outer leaflet of the plasma membrane. This work reveals a mechanism for annexin translocation across membranes which depends on plasma membrane phospholipid flipping.

scholarly journals EPAC1 regulates endothelial Annexin A2 cell surface translocation and plasminogen activation

2017 ◽  
Author(s):  
Wenli Yang ◽  
Fang C. Mei ◽  
Xiaodong Cheng
Keyword(s):  
Endothelial Cells ◽  
Cell Surface ◽  
Critical Role ◽  
Annexin A2 ◽  
Plasminogen Activation ◽  
Endothelial Cell Surface ◽  
Cellular Processes ◽  
Wide Range ◽  
Tissue Plasminogen ◽  
Surface Translocation

ABSTRACTAnnexins, a family of highly conserved calcium-and phospholipid-binding proteins, play important roles in a wide range of physiological functions. Among the twelve known annexins in human, Annexin A2 (AnxA2) is one of the most extensively studied and has been implicated in various human diseases. AnxA2 can exist as a monomer or a heterotetrameric complex with S100A10 (P11) and plays a critical role in many cellular processes including exocytosis/endocytosis and membrane organization. At the endothelial cell surface, (AnxA2•P11)2 tetramer, acting as a coreceptor for plasminogen and tissue plasminogen activator (t-PA), accelerates t-PA dependent activation of the fibrinolytic protease, plasmin, the enzyme responsible for thrombus dissolution and degradation of fibrin. This study shows that exchange proteins directly activated by cAMP isoform 1 (EPAC1) interacts with AnxA2 and regulates its biological functions by modulating its membrane translocation in endothelial cells. Using genetic and pharmacological approaches, it is demonstrated that EPAC1, acting through the PLCε-PKC pathway, inhibits AnxA2 surface translocation and plasminogen activation. These results suggest that EPAC1 plays a role in the regulation of fibrinolysis in endothelial cells and may represent a novel therapeutic target for disorders of fibrinolysis.

Effect of Lipoprotein(a) and LDL on Plasminogen Binding to Extracellular Matrix and on Matrix-dependent Plasminogen Activation by Tissue Plasminogen Activator

1996 ◽  
Vol 75 (03) ◽  
pp. 497-502 ◽  
Author(s):  
Hadewijch L M Pekelharing ◽  
Henne A Kleinveld ◽  
Pieter F C.C.M Duif ◽  
Bonno N Bouma ◽  
Herman J M van Rijn
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Binding Sites ◽  
Umbilical Vein ◽  
Single Step ◽  
Plasminogen Activation ◽  
Structural Homology ◽  
Tissue Plasminogen ◽  
Umbilical Vein Endothelial Cells

SummaryLp(a) is an LDL-like lipoprotein plus an additional apolipoprotein apo(a). Based on the structural homology of apo(a) with plasminogen, it is hypothesized that Lp(a) interferes with fibrinolysis. Extracellular matrix (ECM) produced by human umbilical vein endothelial cells was used to study the effect of Lp(a) and LDL on plasminogen binding and activation. Both lipoproteins were isolated from the same plasma in a single step. Plasminogen bound to ECM via its lysine binding sites. Lp(a) as well as LDL were capable of competing with plasminogen binding. The degree of inhibition was dependent on the lipoprotein donor as well as the ECM donor. When Lp(a) and LDL obtained from one donor were compared, Lp(a) was always a much more potent competitor. The effect of both lipoproteins on plasminogen binding was reflected in their effect on plasminogen activation. It is speculated that Lp(a) interacts with ECM via its LDL-like lipoprotein moiety as well as via its apo(a) moiety.

scholarly journals Tissue plasminogen activator is a ligand of cation-independent mannose 6-phosphate receptor and consists of glycoforms that contain mannose 6-phosphate

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James J. Miller ◽  
Richard N. Bohnsack ◽  
Linda J. Olson ◽  
Mayumi Ishihara ◽  
Kazuhiro Aoki ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Dependent Manner ◽  
Plasminogen Activation ◽  
Urokinase Plasminogen Activator Receptor ◽  
Plasminogen Activation System ◽  
Extracellular Region ◽  
Glycosylation Sites ◽  
Tissue Plasminogen ◽  
Mannose 6 Phosphate

AbstractPlasmin is the key enzyme in fibrinolysis. Upon interaction with plasminogen activators, the zymogen plasminogen is converted to active plasmin. Some studies indicate plasminogen activation is regulated by cation-independent mannose 6-phosphate receptor (CI-MPR), a protein that facilitates lysosomal enzyme trafficking and insulin-like growth factor 2 downregulation. Plasminogen regulation may be accomplished by CI-MPR binding to plasminogen or urokinase plasminogen activator receptor. We asked whether other members of the plasminogen activation system, such as tissue plasminogen activator (tPA), also interact with CI-MPR. Because tPA is a glycoprotein with three N-linked glycosylation sites, we hypothesized that tPA contains mannose 6-phosphate (M6P) and binds CI-MPR in a M6P-dependent manner. Using surface plasmon resonance, we found that two sources of tPA bound the extracellular region of human and bovine CI-MPR with low-mid nanomolar affinities. Binding was partially inhibited with phosphatase treatment or M6P. Subsequent studies revealed that the five N-terminal domains of CI-MPR were sufficient for tPA binding, and this interaction was also partially mediated by M6P. The three glycosylation sites of tPA were analyzed by mass spectrometry, and glycoforms containing M6P and M6P-N-acetylglucosamine were identified at position N448 of tPA. In summary, we found that tPA contains M6P and is a CI-MPR ligand.

scholarly journals EPAC1 regulates endothelial annexin A2 cell surface translocation and plasminogen activation

2018 ◽  
Vol 32 (4) ◽  
pp. 2212-2222 ◽  
Author(s):  
Wenli Yang ◽  
Fang C. Mei ◽  
Xiaodong Cheng
Keyword(s):  
Cell Surface ◽  
Annexin A2 ◽  
Plasminogen Activation ◽  
Surface Translocation

The potentiating effect of platelet on plasminogen activation by tissue plasminogen activator

1985 ◽  
Vol 40 (6) ◽  
pp. 853-861 ◽  
Author(s):  
K. Deguchi ◽  
S. Murashima ◽  
S. Shirakawa ◽  
C. Soria ◽  
J. Soria ◽  
...  
Keyword(s):  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Plasminogen Activation ◽  
Tissue Plasminogen

BENEFITS OF NITROGENFIXATION TO THE NITROGENFIXING BACTERIA

2021 ◽  
pp. 42-43
Author(s):  
Shriya Phadnis
Keyword(s):  
Soil Bacteria ◽  
Agricultural Sector ◽  
Nitrogen Starvation ◽  
Review Article ◽  
Symbiotic Association ◽  
Symbiotic Relationship ◽  
Enzymatic Conversion ◽  
Mutualistic Symbiosis ◽  
Biological Nitrogen

The state of some plants being deprived from the availability of nitrogen causing nitrogen starvation leads to the phenomenon of Biological Nitrogen Fixation . Microorganisms are employed to enhance the availability of nitrogen to these plants. The major N2 - xing systems involve the symbiotic association between rhizobia soil bacteria and legumes. The enzymatic conversion of free nitrogen to ammonia occurs as a part of this symbiotic relationship. The signicant role of this phenomenon is enhancing the fertility of the soil and in the growth of the host plant that would otherwise be nitrogen limiting. This process has fascinated researchers in the agricultural sector for the yield of legume crops. This review article focuses on the benets that Rhizobium earns on being in mutualistic symbiosis with the leguminous plants.

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