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Biomolecules Sep 2023S100A10 (p11, annexin II light chain, calpactin light chain) is a multifunctional protein with a wide range of physiological activity. S100A10 is unique among the S100... (Review)
Review
S100A10 (p11, annexin II light chain, calpactin light chain) is a multifunctional protein with a wide range of physiological activity. S100A10 is unique among the S100 family members of proteins since it does not bind to Ca, despite its sequence and structural similarity. This review focuses on studies highlighting the structure, regulation, and binding partners of S100A10. The binding partners of S100A10 were collated and summarized.
Topics: S100 Proteins; Annexin A2; Annexins; Cell Physiological Phenomena
PubMed: 37892132
DOI: 10.3390/biom13101450 -
International Journal of Molecular... Feb 2018Cells respond to pathophysiological states by activation of stress-induced signalling. Regulatory non-coding microRNAs (miRNAs) often form stable feed-forward loops... (Review)
Review
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 Ca, 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.
Topics: Animals; Annexins; Extracellular Vesicles; Humans; MicroRNAs; Signal Transduction; Stress, Physiological
PubMed: 29462943
DOI: 10.3390/ijms19020591 -
The Journal of Clinical Investigation Nov 2019Membrane repair is essential to cell survival. In skeletal muscle, injury often associates with plasma membrane disruption. Additionally, muscular dystrophy is linked to...
Membrane repair is essential to cell survival. In skeletal muscle, injury often associates with plasma membrane disruption. Additionally, muscular dystrophy is linked to mutations in genes that produce fragile membranes or reduce membrane repair. Methods to enhance repair and reduce susceptibility to injury could benefit muscle in both acute and chronic injury settings. Annexins are a family of membrane-associated Ca2+-binding proteins implicated in repair, and annexin A6 was previously identified as a genetic modifier of muscle injury and disease. Annexin A6 forms the repair cap over the site of membrane disruption. To elucidate how annexins facilitate repair, we visualized annexin cap formation during injury. We found that annexin cap size positively correlated with increasing Ca2+ concentrations. We also found that annexin overexpression promoted external blebs enriched in Ca2+ and correlated with a reduction of intracellular Ca2+ at the injury site. Annexin A6 overexpression reduced membrane injury, consistent with enhanced repair. Treatment with recombinant annexin A6 protected against acute muscle injury in vitro and in vivo. Moreover, administration of recombinant annexin A6 in a model of muscular dystrophy reduced serum creatinine kinase, a biomarker of disease. These data identify annexins as mediators of membrane-associated Ca2+ release during membrane repair and annexin A6 as a therapeutic target to enhance membrane repair capacity.
Topics: Animals; Annexin A6; Calcium; Cell Membrane; Female; Male; Mice; Mice, Knockout; Muscle, Skeletal; Muscular Dystrophy, Animal; Recombinant Proteins
PubMed: 31545299
DOI: 10.1172/JCI128840 -
Biochimica Et Biophysica Acta.... Jun 2017Annexin A6 (AnxA6) belongs to the conserved annexin family - a group of Ca-dependent membrane binding proteins. AnxA6 is the largest of all annexins and highly expressed... (Review)
Review
Annexin A6 (AnxA6) belongs to the conserved annexin family - a group of Ca-dependent membrane binding proteins. AnxA6 is the largest of all annexins and highly expressed in smooth muscle, hepatocytes, endothelial cells and cardiomyocytes. Upon activation, AnxA6 binds to negatively charged phospholipids in a wide range of intracellular localizations, in particular the plasma membrane, late endosomes/pre-lysosomes, but also synaptic vesicles and sarcolemma. In these cellular sites, AnxA6 is believed to contribute to the organization of membrane microdomains, such as cholesterol-rich lipid rafts and confer multiple regulatory functions, ranging from vesicle fusion, endocytosis and exocytosis to programmed cell death and muscle contraction. Growing evidence supports that Ca and Ca-binding proteins control endocytosis and autophagy. Their regulatory role seems to operate at the level of the signalling pathways that initiate autophagy or at later stages, when autophagosomes fuse with endolysosomal compartments. The convergence of the autophagic and endocytic vesicles to lysosomes shares several features that depend on Ca originating from lysosomes/late endosomes and seems to depend on proteins that are subsequently activated by this cation. However, the involvement of Ca and its effector proteins in these autophagic and endocytic stages still remains poorly understood. Although AnxA6 makes up almost 0.25% of total protein in the liver, little is known about its function in hepatocytes. Within the endocytic route, we identified AnxA6 in endosomes and autophagosomes of hepatocytes. Hence, AnxA6 and possibly other annexins might represent new Ca effectors that regulate converging steps of autophagy and endocytic trafficking in hepatocytes. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
Topics: Animals; Annexin A6; Cell Compartmentation; Cell Line; Cell Line, Tumor; Endocytosis; Humans; Liver
PubMed: 27984093
DOI: 10.1016/j.bbamcr.2016.10.017 -
Biochimica Et Biophysica Acta Dec 2004Molecular systematic analysis of the annexin gene superfamily characterized the evolutionary origin, frequency and range of structural variation in calcium interaction... (Review)
Review
Molecular systematic analysis of the annexin gene superfamily characterized the evolutionary origin, frequency and range of structural variation in calcium interaction domains that are considered intrinsic for membrane targeting and ion channel function. Approximately 36% of annexin repeat domains in an estimated 100 distinct subfamilies contained amino acid changes consistent with the functional loss of type two calcium-binding sites. At least 11% of annexin domains contained a novel K/H/RGD motif conserved in particular subfamilies and manifest in all phyla, apparently via convergent evolution. The first yeast annexin from Yarrowia lipolytica was classified in the ANXC1 subfamily with fungal and mycetozoan representatives. This clade had intact calcium-binding sites but disruption of the normally well-conserved, mid-repeat 4 region implicated in calcium channel regulation. Conversely, a tandem pair of novel annexins from the amphioxus Branchiostoma floridae resembled annexin A13 in gene structure and conserved the charged amino acids associated with the internal hydrophilic pore, but were devoid of external type 2 calcium-binding sites and incorporated K/RGD motifs instead, like annexin A9. The selective erosion of calcium-binding sites in annexin domains and the occurrence of alternate ligands in the same exposed, interhelical loops are pervasive features of the superfamily. This suggests greater complexity than previously appreciated in the mechanisms controlling annexin membrane interaction and calcium channel operation.
Topics: Amino Acid Sequence; Animals; Annexins; Binding Sites; Calcium; Humans; Molecular Sequence Data; Phylogeny
PubMed: 15590063
DOI: 10.1016/j.bbamcr.2004.09.010 -
Biochimica Et Biophysica Acta Jun 2008In normal healthy cells phosphatidylserine is located in the inner leaflet of the plasma membrane. However, on activated platelets, dying cells and under specific... (Review)
Review
In normal healthy cells phosphatidylserine is located in the inner leaflet of the plasma membrane. However, on activated platelets, dying cells and under specific circumstances also on various types of viable leukocytes phosphatidylserine is actively externalized to the outer leaflet of the plasma membrane. Annexin A5 has the ability to bind in a calcium-dependent manner to phosphatidylserine and to form a membrane-bound two-dimensional crystal lattice. Based on these abilities various functions for extracellular annexin A5 on the phosphatidylserine-expressing plasma membrane have been proposed. In this review we describe possible mechanisms for externalization of annexin A5 and various processes in which extracellular annexin A5 may play a role such as blood coagulation, apoptosis, phagocytosis and formation of plasma membrane-derived microparticles. We further highlight the recent discovery of internalization of extracellular annexin A5 by phosphatidylserine-expressing cells.
Topics: Annexin A5; Apoptosis; Cell Membrane; Crystallization; Humans; Phagocytosis; Phosphatidylserines
PubMed: 18334229
DOI: 10.1016/j.bbamcr.2008.01.030 -
International Journal of Molecular... Jul 2019Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to... (Review)
Review
Obesity and the associated comorbidities are a growing health threat worldwide. Adipose tissue dysfunction, impaired adipokine activity, and inflammation are central to metabolic diseases related to obesity. In particular, the excess storage of lipids in adipose tissues disturbs cellular homeostasis. Amongst others, organelle function and cell signaling, often related to the altered composition of specialized membrane microdomains (lipid rafts), are affected. Within this context, the conserved family of annexins are well known to associate with membranes in a calcium (Ca)- and phospholipid-dependent manner in order to regulate membrane-related events, such as trafficking in endo- and exocytosis and membrane microdomain organization. These multiple activities of annexins are facilitated through their diverse interactions with a plethora of lipids and proteins, often in different cellular locations and with consequences for the activity of receptors, transporters, metabolic enzymes, and signaling complexes. While increasing evidence points at the function of annexins in lipid homeostasis and cell metabolism in various cells and organs, their role in adipose tissue, obesity and related metabolic diseases is still not well understood. Annexin A1 (AnxA1) is a potent pro-resolving mediator affecting the regulation of body weight and metabolic health. Relevant for glucose metabolism and fatty acid uptake in adipose tissue, several studies suggest AnxA2 to contribute to coordinate glucose transporter type 4 (GLUT4) translocation and to associate with the fatty acid transporter CD36. On the other hand, AnxA6 has been linked to the control of adipocyte lipolysis and adiponectin release. In addition, several other annexins are expressed in fat tissues, yet their roles in adipocytes are less well examined. The current review article summarizes studies on the expression of annexins in adipocytes and in obesity. Research efforts investigating the potential role of annexins in fat tissue relevant to health and metabolic disease are discussed.
Topics: Adipocytes; Adipose Tissue; Animals; Annexins; Biomarkers; Disease Susceptibility; Gene Expression Regulation; Glucose; Humans; Insulin; Lipid Metabolism; Obesity
PubMed: 31337068
DOI: 10.3390/ijms20143449 -
Traffic (Copenhagen, Denmark) Aug 2007Annexins are calcium- and phospholipid-binding proteins that have been proposed to have multiple roles in membrane traffic. Historically, this has been based on the in... (Review)
Review
Annexins are calcium- and phospholipid-binding proteins that have been proposed to have multiple roles in membrane traffic. Historically, this has been based on the in vitro properties of annexins and their localization to specific membrane compartments. However, recent functional evidence supports a role for annexins in specific membrane traffic steps, although the requirement for annexins may be highly dependent on the cellular context. Here we review the roles of annexins in traffic within the endocytic pathway, focusing on clathrin-dependent internalization from the plasma membrane, multivesicular endosome/body (MVB) biogenesis and MVB-lysosome fusion.
Topics: Animals; Annexins; Endocytosis; Humans
PubMed: 17547702
DOI: 10.1111/j.1600-0854.2007.00590.x -
Journal of Cellular and Molecular... Aug 2022Annexin-1 (ANXA1) is widely reported to be deregulated in various cancers and is involved in tumorigenesis. However, its effects on glioblastoma (GBM) remain unclear....
Annexin-1 (ANXA1) is widely reported to be deregulated in various cancers and is involved in tumorigenesis. However, its effects on glioblastoma (GBM) remain unclear. Using immunohistochemistry with tissue microarrays, we showed that ANXA1 was overexpressed in GBM, positively correlated with higher World Health Organization (WHO) grades of glioma, and negatively associated with poor survival. To further explore its role and the underlying molecular mechanism in GBM, we constructed ANXA1shRNA U87 and U251 cell lines for further experiments. ANXA1 downregulation suppressed GBM cell proliferation, migration, and invasion and enhanced their radiosensitivity. Furthermore, we determined that ANXA1 was involved in dendritic cell (DC) maturation in patients with GBM and that DC infiltration was inversely proportional to GBM prognosis. Considering that previous reports have shown that Interleukin-8 (IL-8) is associated with DC migration and maturation and is correlated with NF-κB transcriptional regulation, we examined IL-8 and p65 subunit expressions and p65 phosphorylation levels in GBM cells under an ANXA1 knockdown. These results suggest that ANXA1 significantly promotes IL-8 production and p65 phosphorylation levels. We inferred that ANXA1 is a potential biomarker and a candidate therapeutic target for GBM treatment and may mediate tumour immune escape through NF-kB (p65) activation and IL-8 upregulation.
Topics: Annexin A1; Annexins; Brain Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioblastoma; Humans; Interleukin-8; NF-kappa B; Oncogenes; Tumor Escape; Up-Regulation
PubMed: 35770335
DOI: 10.1111/jcmm.17458 -
Acta Tropica Jul 2023Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated... (Review)
Review
Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies.
Topics: Animals; Humans; Annexins; Parasitic Diseases; Protozoan Infections; Malaria; Leishmaniasis; Parasites
PubMed: 37172709
DOI: 10.1016/j.actatropica.2023.106942