Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Annexins—Closing the Gap between Fundamental and Translational Research

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2017) | Viewed by 63792

Share This Special Issue

Special Issue Editors

Prof. Dr. Ursula Rescher

E-Mail Website
Guest Editor

Institute of Medical Biochemistry, Center for Molecular Biology of Inflammation, University of Münster, Von-Esmarch-Straße 56, D-48149 Münster, Germany
Interests: host–pathogen interactions; host intracellular compartments; drug repurposing
Special Issues, Collections and Topics in MDPI journals

Dr. Thomas Grewal

E-Mail Website
Guest Editor

School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, Australia
Interests: role of annexin A6 and LDL-cholesterol export from late endosomes in health and disease; LDL-cholesterol and cancer cell growth, migration and invasion; cholesterol and formation of membrane contact sites; lipid accumulation, obesity and anti-cancer drug performance; annexins in endo- and exocytosis; EGFR/Ras signalling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

After their discovery, more than 4 decades ago, and the detailed characterization of their structural and functional properties over the years, it is now well believed that annexins have a wide variety of critical cellular functions, often related to human diseases. Highlighting some of the current hot topics in annexin research, a variety of contributions in this Special Issue first underscore the major gaps and lack of molecular insights related to certain biomedical research areas. Each article is centered around an individual member of the annexin family, identifying them as key players in a variety of human diseases. Moreover, the combination of molecular, cell- and animal-based studies with patient data identify several annexin-targeted approaches being highly relevant for translational research. This Special Issue is not aiming for a comprehensive overview of annexin research, but rather aims to provide some recent developments in this field. We believe that the readership of your journal, and basic, as well as clinically-orientated, researchers interested in molecular sciences, would greatly benefit from this Special Issue that summarizes and comments on recent findings from several annexin laboratories.

Prof. Ursula Rescher
Prof. Thomas Grewal
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

annexins
membrane transport
cell signaling
extracellular properties
cancer
inflammatory diseases
atherosclerosis

Published Papers (10 papers)

Download All Papers

Research

Jump to: Review

11 pages, 2953 KiB

Open AccessArticle

The Annexin A1 Receptor FPR2 Regulates the Endosomal Export of Influenza Virus

by Fryad Rahman, Mohammad Chebbo, Noémie Courtin, Aurelien Fotso Fotso, Marie-Christine Alessi and Béatrice Riteau

Int. J. Mol. Sci. 2018, 19(5), 1400; https://doi.org/10.3390/ijms19051400 - 08 May 2018

Cited by 10 | Viewed by 5207

Abstract

The Formyl Peptide Receptor 2 (FPR2) is a novel promising target for the treatment of influenza. During viral infection, FPR2 is activated by annexinA1, which is present in the envelope of influenza viruses; this activation promotes virus replication. Here, we investigated whether blockage of FPR2 would affect the genome trafficking of influenza virus. We found that, upon infection and cell treatment with the specific FPR2 antagonist WRW4 or the anti-FPR2 monoclonal antibody, FN-1D6-AI, influenza viruses were blocked into endosomes. This effect was independent on the strain and was observed for H1N1 and H3N2 viruses. In addition, blocking FPR2signaling in alveolar lung A549 epithelial cells with the monoclonal anti-FPR2 antibody significantly inhibited virus replication. Altogether, these results show that FPR2signaling interferes with the endosomal trafficking of influenza viruses and provides, for the first time, the proof of concept that monoclonal antibodies directed against FPR2 inhibit virus replication. Antibodies-based therapeutics have emerged as attractive reagents in infectious diseases. Thus, this study suggests that the use of anti-FPR2 antibodies against influenza hold great promise for the future. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Graphical abstract

5303 KiB

Open AccessArticle

Ac2-26, an Annexin A1 Peptide, Attenuates Ischemia-Reperfusion-Induced Acute Lung Injury

by Wen-I Liao, Shu-Yu Wu, Geng-Chin Wu, Hsin-Ping Pao, Shih-En Tang, Kun-Lun Huang and Shi-Jye Chu

Int. J. Mol. Sci. 2017, 18(8), 1771; https://doi.org/10.3390/ijms18081771 - 15 Aug 2017

Cited by 43 | Viewed by 5893 | Correction

Abstract

Annexin A1 (AnxA1) is an endogenous protein that modulates anti-inflammatory processes, and its therapeutic potential has been reported in a range of inflammatory diseases. The effect of AnxA1 on ischemia-reperfusion (IR)-induced lung injury has not been examined. In this study, isolated, perfused rat lungs were subjected to IR lung injury induced by ischemia for 40 min, followed by reperfusion for 60 min. The rat lungs were randomly treated with vehicle (phosphate-buffered saline), and Ac2-26 (an active N-terminal peptide of AnxA1) with or without an N-formyl peptide receptor (FPR) antagonist N-Boc-Phe-Leu-Phe-Leu-Phe (Boc2). An in vitro study of the effects of Ac2-26 on human alveolar epithelial cells subjected to hypoxia-reoxygenation was also investigated. Administration of Ac2-26 in IR lung injury produced a significant attenuation of lung edema, pro-inflammatory cytokine production recovered in bronchoalveolar lavage fluid, oxidative stress, apoptosis, neutrophil infiltration, and lung tissue injury. Ac2-26 also decreased AnxA1 protein expression, inhibited the activation of nuclear factor-κB and mitogen-activated protein kinase pathways in the injured lung tissue. Finally, treatment with Boc2 abolished the protective action of Ac2-26. The results indicated that Ac2-26 had a protective effect against acute lung injury induced by IR, which may be via the activation of the FPR. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 697 KiB

Open AccessReview

Annexins in Translational Research: Hidden Treasures to Be Found

by Sebastian Schloer, Denise Pajonczyk and Ursula Rescher

Int. J. Mol. Sci. 2018, 19(6), 1781; https://doi.org/10.3390/ijms19061781 - 15 Jun 2018

Cited by 57 | Viewed by 4907

Abstract

The vertebrate annexin superfamily (AnxA) consists of 12 members of a calcium (Ca²⁺) and phospholipid binding protein family which share a high structural homology. In keeping with this hallmark feature, annexins have been implicated in the Ca²⁺-controlled regulation of a broad range of membrane events. In this review, we identify and discuss several themes of annexin actions that hold a potential therapeutic value, namely, the regulation of the immune response and the control of tissue homeostasis, and that repeatedly surface in the annexin activity profile. Our aim is to identify and discuss those annexin properties which might be exploited from a translational science and specifically, a clinical point of view. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Figure 1

11 pages, 220 KiB

Open AccessReview

Regulation of von-Willebrand Factor Secretion from Endothelial Cells by the Annexin A2-S100A10 Complex

by Anna Holthenrich and Volker Gerke

Int. J. Mol. Sci. 2018, 19(6), 1752; https://doi.org/10.3390/ijms19061752 - 13 Jun 2018

Cited by 26 | Viewed by 3880

Abstract

Endothelial cells serve as gatekeepers of vascular hemostasis and local inflammatory reactions. They can rapidly respond to changes in the environment, caused, for example, by blood vessel injury, tissue damage or infection, by secreting in a strictly regulated manner factors regulating these processes. These factors include adhesion receptors for circulating leukocytes and platelets, P-selectin and von-Willebrand factor (VWF) that are stored in specialized secretory granules of endothelial cells, the Weibel-Palade bodies (WPB). Acute exposure of these adhesion molecules converts the endothelial cell surface from an anti-adhesive state enabling unrestricted flow of circulating blood cells to an adhesive one capable of capturing leukocytes (through P-selectin) and platelets (through VWF). While these are important (patho)physiological responses, compromised or dysregulated WPB secretion can cause pathologies such as excessive bleeding or vascular occlusion. Several factors are involved in regulating the exocytosis of WPB and thus represent potential targets for therapeutic interventions in these pathologies. Among them, the annexin A2 (AnxA2)-S100A10 complex has been shown to participate in the tethering/docking of secretion-competent WPB at the plasma membrane, and interference with AnxA2/S100A10 expression or complex formation significantly reduces acute WPB exocytosis and VWF release. Thus, developing specific means to efficiently block AnxA2-S100A10 complex formation in endothelial cells could lead to novel avenues towards interfering with acute vascular thrombosis. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

25 pages, 1417 KiB

Open AccessReview

Annexins—Coordinators of Cholesterol Homeostasis in Endocytic Pathways

by Carles Rentero, Patricia Blanco-Muñoz, Elsa Meneses-Salas, Thomas Grewal and Carlos Enrich

Int. J. Mol. Sci. 2018, 19(5), 1444; https://doi.org/10.3390/ijms19051444 - 12 May 2018

Cited by 41 | Viewed by 7616

Abstract

The spatiotemporal regulation of calcium (Ca²⁺) storage in late endosomes (LE) and lysosomes (Lys) is increasingly recognized to influence a variety of membrane trafficking events, including endocytosis, exocytosis, and autophagy. Alterations in Ca²⁺ homeostasis within the LE/Lys compartment are implicated in human diseases, ranging from lysosomal storage diseases (LSDs) to neurodegeneration and cancer, and they correlate with changes in the membrane binding behaviour of Ca²⁺-binding proteins. This also includes Annexins (AnxA), which is a family of Ca²⁺-binding proteins participating in membrane traffic and tethering, microdomain organization, cytoskeleton interactions, Ca²⁺ signalling, and LE/Lys positioning. Although our knowledge regarding the way Annexins contribute to LE/Lys functions is still incomplete, recruitment of Annexins to LE/Lys is greatly influenced by the availability of Annexin bindings sites, including acidic phospholipids, such as phosphatidylserine (PS) and phosphatidic acid (PA), cholesterol, and phosphatidylinositol (4,5)-bisphosphate (PIP2). Moreover, the cytosolic portion of LE/Lys membrane proteins may also, directly or indirectly, determine the recruitment of Annexins to LE. Strikingly, within LE/Lys, AnxA1, A2, A6, and A8 differentially contribute to cholesterol transport along the endocytic route, in particular, cholesterol transfer between LE and other compartments, positioning Annexins at the centre of major pathways mediating cellular cholesterol homeostasis. Underlying mechanisms include the formation of membrane contact sites (MCS) and intraluminal vesicles (ILV), as well as the modulation of LE-cholesterol transporter activity. In this review, we will summarize the current understanding how Annexins contribute to influence LE/Lys membrane transport and associated functions. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Graphical abstract

13 pages, 987 KiB

Open AccessReview

Annexin A1 and Autoimmunity: From Basic Science to Clinical Applications

by Maurizio Bruschi, Andrea Petretto, Augusto Vaglio, Laura Santucci, Giovanni Candiano and Gian Marco Ghiggeri

Int. J. Mol. Sci. 2018, 19(5), 1348; https://doi.org/10.3390/ijms19051348 - 03 May 2018

Cited by 42 | Viewed by 5268

Abstract

Annexin A1 is a protein with multifunctional roles in innate and adaptive immunity mainly devoted to the regulation of inflammatory cells and the resolution of inflammation. Most of the data regarding Annexin A1 roles in immunity derive from cell studies and from mice models lacking Annexin A1 for genetic manipulation (Annexin A1^−/−); only a few studies sought to define how Annexin A1 is involved in human diseases. High levels of anti-Annexin A1 autoantibodies have been reported in systemic lupus erythematosus (SLE), suggesting this protein is implicated in auto-immunity. Here, we reviewed the evidence available for an association of anti-Annexin A1 autoantibodies and SLE manifestations, in particular in those cases complicated by lupus nephritis. New studies show that serum levels of Annexin A1 are increased in patients presenting renal complications of SLE, but this increment does not correlate with circulating anti-Annexin A1 autoantibodies. On the other hand, high circulating Annexin A1 levels cannot explain per se the development of autoantibodies since post-translational modifications are necessary to make a protein immunogenic. A hypothesis is presented here and discussed regarding the possibility that Annexin A1 undergoes post-translational modifications as a part of neutrophil extracellular traps (NETs) that are produced in response to viral, bacterial, and/or inflammatory triggers. In particular, focus is on the process of citrullination of Annexin A1, which takes place within NETs and that mimics, to some extent, other autoimmune conditions, such as rheumatoid arthritis, that are characterized by the presence of anti-citrullinated peptides in circulation. The description of pathologic pathways leading to modification of Annexin A1 as a trigger of autoimmunity is a cognitive evolution, but requires more experimental data before becoming a solid concept for explaining autoimmunity in human beings. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Figure 1

18 pages, 17641 KiB

Open AccessReview

Annexins in Glaucoma

by Timothy E. Yap, Benjamin Michael Davis, Li Guo, Eduardo M. Normando and Maria Francesca Cordeiro

Int. J. Mol. Sci. 2018, 19(4), 1218; https://doi.org/10.3390/ijms19041218 - 17 Apr 2018

Cited by 13 | Viewed by 4807

Abstract

Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Figure 1

19 pages, 1975 KiB

Open AccessReview

Therapeutic Potential of Annexin A1 in Ischemia Reperfusion Injury

by Junaid Ansari, Gaganpreet Kaur and Felicity N. E. Gavins

Int. J. Mol. Sci. 2018, 19(4), 1211; https://doi.org/10.3390/ijms19041211 - 16 Apr 2018

Cited by 51 | Viewed by 5817

Abstract

Cardiovascular disease (CVD) continues to be the leading cause of death in the world. Increased inflammation and an enhanced thrombotic milieu represent two major complications of CVD, which can culminate into an ischemic event. Treatment for these life-threatening complications remains reperfusion and restoration of blood flow. However, reperfusion strategies may result in ischemia–reperfusion injury (I/RI) secondary to various cardiovascular pathologies, including myocardial infarction and stroke, by furthering the inflammatory and thrombotic responses and delivering inflammatory mediators to the affected tissue. Annexin A1 (AnxA1) and its mimetic peptides are endogenous anti-inflammatory and pro-resolving mediators, known to have significant effects in resolving inflammation in a variety of disease models. Mounting evidence suggests that AnxA1, which interacts with the formyl peptide receptor (FPR) family, may have a significant role in mitigating I/RI associated complications. In this review article, we focus on how AnxA1 plays a protective role in the I/R based vascular pathologies. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Figure 1

20 pages, 9160 KiB

Open AccessReview

Annexin A1: Uncovering the Many Talents of an Old Protein

by Madeeha H. Sheikh and Egle Solito

Int. J. Mol. Sci. 2018, 19(4), 1045; https://doi.org/10.3390/ijms19041045 - 31 Mar 2018

Cited by 128 | Viewed by 14610

Abstract

Annexin A1 (ANXA1) has long been classed as an anti-inflammatory protein due to its control over leukocyte-mediated immune responses. However, it is now recognized that ANXA1 has widespread effects beyond the immune system with implications in maintaining the homeostatic environment within the entire body due to its ability to affect cellular signalling, hormonal secretion, foetal development, the aging process and development of disease. In this review, we aim to provide a global overview of the role of ANXA1 covering aspects of peripheral and central inflammation, immune repair and endocrine control with focus on the prognostic, diagnostic and therapeutic potential of the molecule in cancer, neurodegeneration and inflammatory-based disorders. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures

Figure 1

21 pages, 2446 KiB

Open AccessReview

Functional Association between Regulatory RNAs and the Annexins

by Katia Monastyrskaya

Int. J. Mol. Sci. 2018, 19(2), 591; https://doi.org/10.3390/ijms19020591 - 16 Feb 2018

Cited by 25 | Viewed by 4919

Abstract

Cells respond to pathophysiological states by activation of stress-induced signalling. Regulatory non-coding microRNAs (miRNAs) often form stable feed-forward loops which ensure prolongation of the signal, contributing to sustained activation. Members of the annexin protein family act as sensors for Ca²⁺, pH, and lipid second messengers, and regulate various signalling pathways. Recently, annexins were reported to participate in feedback loops, suppressing miRNA synthesis and attenuating stress-induced dysregulation of gene expression. They can directly or indirectly associate with RNAs, and are transferred between the cells in exosomes and shed microvesicles. The ability of annexins to recruit other proteins and miRNAs into exosomes implicates them in control of cell–cell interactions, affecting the adaptive responses and remodelling processes during disease. The studies summarized in this Review point to an emerging role of annexins in influencing the synthesis, localisation, and transfer of regulatory RNAs. Full article

(This article belongs to the Special Issue Annexins—Closing the Gap between Fundamental and Translational Research)

► Show Figures