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Nature Microbiology Nov 2022Members of Apicomplexa are defined by apical cytoskeletal structures and secretory organelles, tailored for motility, invasion and egress. Gliding is powered by...
Members of Apicomplexa are defined by apical cytoskeletal structures and secretory organelles, tailored for motility, invasion and egress. Gliding is powered by actomyosin-dependent rearward translocation of apically secreted transmembrane adhesins. In the human parasite Toxoplasma gondii, the conoid, composed of tubulin fibres and preconoidal rings (PCRs), is a dynamic organelle of undefined function. Here, using ultrastructure expansion microscopy, we established that PCRs serve as a hub for glideosome components including Formin1. We also identified components of the PCRs conserved in Apicomplexa, Pcr4 and Pcr5, that contain B-box zinc-finger domains, assemble in heterodimer and are essential for the formation of the structure. The fitness conferring Pcr6 tethers the PCRs to the cone of tubulin fibres. F-actin produced by Formin1 is used by Myosin H to generate the force for conoid extrusion which directs the flux of F-actin to the pellicular space, serving as gatekeeper to control parasite motility.
Topics: Humans; Actins; Cytoskeleton; Protozoan Proteins; Toxoplasma; Tubulin; Apicomplexa
PubMed: 36109645
DOI: 10.1038/s41564-022-01212-x -
The Journal of Cell Biology Sep 2023Apical constriction is a cell shape change that drives key morphogenetic events during development, including gastrulation and neural tube formation. The forces driving...
Apical constriction is a cell shape change that drives key morphogenetic events during development, including gastrulation and neural tube formation. The forces driving apical constriction are primarily generated through the contraction of apicolateral and/or medioapical actomyosin networks. In the Drosophila ventral furrow, the medioapical actomyosin network has a sarcomere-like architecture, with radially polarized actin filaments and centrally enriched non-muscle myosin II and myosin activating kinase. To determine if this is a broadly conserved actin architecture driving apical constriction, we examined actomyosin architecture during C. elegans gastrulation, in which two endodermal precursor cells internalize from the surface of the embryo. Quantification of protein localization showed that neither the non-muscle myosin II NMY-2 nor the myosin-activating kinase MRCK-1 is enriched at the center of the apex. Further, visualization of barbed- and pointed-end capping proteins revealed that actin filaments do not exhibit radial polarization at the apex. Our results demonstrate that C. elegans endodermal precursor cells apically constrict using a mixed-polarity actin filament network and with myosin and a myosin activator distributed throughout the network. Taken together with observations made in other organisms, our results demonstrate that diverse actomyosin architectures are used in animal cells to accomplish apical constriction.
Topics: Animals; Actin Cytoskeleton; Actomyosin; Caenorhabditis elegans; Constriction; Morphogenesis; Myosin Type II; Myosins; Caenorhabditis elegans Proteins
PubMed: 37351566
DOI: 10.1083/jcb.202302102 -
Biomolecules Jun 2020Some beneficial effects of grape seed proanthocyanidin extract (GSPE) can be explained by the modulation of enterohormone secretion. As GSPE comprises a combination of...
Some beneficial effects of grape seed proanthocyanidin extract (GSPE) can be explained by the modulation of enterohormone secretion. As GSPE comprises a combination of different molecules, the pure compounds that cause these effects need to be elucidated. The enterohormones and chemoreceptors present in the gastrointestinal tract differ between species, so if humans are to gain beneficial effects, species closer to humans-and humans themselves-must be used. We demonstrate that 100 mg/L of GSPE stimulates peptide YY (PYY) release, but not glucagon-like peptide 1 (GLP-1) release in the human colon. We used a pig ex vivo system that differentiates between apical and basolateral intestinal sides to analyse how apical stimulation with GSPE and its pure compounds affects the gastrointestinal tract. In pigs, apical GSPE treatment stimulates the basolateral release of PYY in the duodenum and colon and that of GLP-1 in the ascending, but not the descending colon. In the duodenum, luminal stimulation with procyanidin dimer B2 increased PYY secretion, but not CCK secretion, while catechin monomers (catechin/epicatechin) significantly increased CCK release, but not PYY release. The differential effects of GSPE and its pure compounds on enterohormone release at the same intestinal segment suggest that they act through chemosensors located apically and unevenly distributed along the gastrointestinal tract.
Topics: Animals; Cholecystokinin; Gastrointestinal Tract; Glucagon-Like Peptide 1; Humans; Peptide YY; Plant Extracts; Proanthocyanidins; Seeds; Swine; Vitis
PubMed: 32492958
DOI: 10.3390/biom10060844 -
Dental Clinics of North America Jan 2020Periapical pathoses represent changes noted at the apices of teeth within the alveolar process that are suspected on examination, visualized via imaging, and confirmed... (Review)
Review
Periapical pathoses represent changes noted at the apices of teeth within the alveolar process that are suspected on examination, visualized via imaging, and confirmed via histopathology. They can be bone forming or destructive. There are pathologic entities that show both types of changes at the apical regions. These lesions must be identified if they are odontogenic in origin because treatment modalities differ. This article discusses identification of radiopaque and radiolucent lesions noted on radiographs. The common opacities and lucencies are described. When required, advanced imaging is used to depict changes within the bone near the periapical regions of mandibular and maxillary teeth.
Topics: Alveolar Process; Diagnosis, Differential; Humans; Mandible; Tooth
PubMed: 31735225
DOI: 10.1016/j.cden.2019.08.010 -
European Endodontic Journal Apr 2021Apical fenestration describes a window-like opening of the alveolar bone that involves the root apex of the associated tooth. Mucosal fenestration is a similar defect of... (Review)
Review
Apical fenestration describes a window-like opening of the alveolar bone that involves the root apex of the associated tooth. Mucosal fenestration is a similar defect of the overlying mucosa and, when presented with a concomitant apical fenestration, may expose the root apex to the oral environment. A fenestration may arise from physiological and pathological processes. Although its presence does not necessitate treatment per se, these lesions have significant clinical implications when associated with endodontic diseases. Apical fenestrations associated with endodontic infections are relatively uncommon and can easily be overlooked or misdiagnosed. A thorough understanding of these lesions is key for timely diagnosis and successful management. The aim of this study was to review the epidemiology, aetiological factors, characteristics, management methods and potential outcomes of apical fenestrations associated with endodontic diseases. A search of online databases for relevant studies was conducted. With the inclusion of hand searched articles, 20 articles, consisting of case reports and series, were identified, and the key characteristics of each case were summarised. Apical fenestrations were found to be most commonly associated with maxillary teeth and almost always occur on the buccal aspect of the alveolar bone. Clinicians may consider the possibility of an apical fenestration with concurrent endodontic pathology when patients present with non-healing sinus tracts, exposed tooth apices and/or persistent pain after endodontic treatment, particularly on palpation and mastication. Clinical signs and symptoms can vary, hence cone-beam computed tomography is an important tool for diagnosis. The management involves surgically restoring a favourable anatomical configuration of the root apex in relation to the alveolar bony housing and may be combined with guided tissue regeneration and/or grafting procedures. Sloughing, reopening and infection are potential complications. The literature on apical fenestrations associated with endodontic diseases is limited, thus further research is needed to develop evidence-based guidelines for the diagnosis and management of these lesions.
Topics: Cone-Beam Computed Tomography; Dental Pulp Diseases; Guided Tissue Regeneration; Humans; Tooth Apex
PubMed: 33609018
DOI: 10.14744/eej.2020.51422 -
Proceedings of the National Academy of... Oct 2023In various epithelial tissues, the epithelial monolayer acts as a barrier. To fulfill its function, the structural integrity of the epithelium is tightly controlled....
In various epithelial tissues, the epithelial monolayer acts as a barrier. To fulfill its function, the structural integrity of the epithelium is tightly controlled. When normal epithelial cells detach from the basal substratum and delaminate into the apical lumen, the apically extruded cells undergo apoptosis, which is termed anoikis. In contrast, transformed cells often become resistant to anoikis and able to survive and grow in the apical luminal space, leading to the formation of multilayered structures, which can be observed at the early stage of carcinogenesis. However, the underlying molecular mechanisms still remain elusive. In this study, we first demonstrate that S100A10 and ANXA2 (Annexin A2) accumulate in apically extruded, transformed cells in both various cell culture systems and murine epithelial tissues in vivo. ANXA2 acts upstream of S100A10 accumulation. Knockdown of ANXA2 promotes apoptosis of apically extruded RasV12-transformed cells and suppresses the formation of multilayered epithelia. In addition, the intracellular reactive oxygen species (ROS) are elevated in apically extruded RasV12 cells. Treatment with ROS scavenger Trolox reduces the occurrence of apoptosis of apically extruded ANXA2-knockdown RasV12 cells and restores the formation of multilayered epithelia. Furthermore, ROS-mediated p38MAPK activation is observed in apically delaminated RasV12 cells, and ANXA2 knockdown further enhances the p38MAPK activity. Moreover, the p38MAPK inhibitor promotes the formation of multilayered epithelia of ANXA2-knockdown RasV12 cells. These results indicate that accumulated ANXA2 diminishes the ROS-mediated p38MAPK activation in apically extruded transformed cells, thereby blocking the induction of apoptosis. Hence, ANXA2 can be a potential therapeutic target to prevent multilayered, precancerous lesions.
Topics: Animals; Mice; Annexin A2; Apoptosis; Epithelial Cells; Epithelium; Reactive Oxygen Species
PubMed: 37844241
DOI: 10.1073/pnas.2307118120 -
Current Biology : CB Feb 2020When oncogenic transformation or apoptosis occurs within epithelia, the harmful or dead cells are apically extruded from tissues to maintain epithelial homeostasis....
When oncogenic transformation or apoptosis occurs within epithelia, the harmful or dead cells are apically extruded from tissues to maintain epithelial homeostasis. However, the underlying molecular mechanism still remains elusive. In this study, we first show, using mammalian cultured epithelial cells and zebrafish embryos, that prior to apical extrusion of RasV12-transformed cells, calcium wave occurs from the transformed cell and propagates across the surrounding cells. The calcium wave then triggers and facilitates the process of extrusion. IP receptor, gap junction, and mechanosensitive calcium channel TRPC1 are involved in calcium wave. Calcium wave induces the polarized movement of the surrounding cells toward the extruding transformed cells. Furthermore, calcium wave facilitates apical extrusion, at least partly, by inducing actin rearrangement in the surrounding cells. Moreover, comparable calcium propagation also promotes apical extrusion of apoptotic cells. Thus, calcium wave is an evolutionarily conserved, general regulatory mechanism of cell extrusion.
Topics: Animals; Calcium Signaling; Cell Transformation, Neoplastic; Dogs; Embryo, Nonmammalian; Madin Darby Canine Kidney Cells; Zebrafish
PubMed: 32004455
DOI: 10.1016/j.cub.2019.11.089 -
Acta Physiologica (Oxford, England) May 2023Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the... (Review)
Review
Central to the maintenance of calcium homeostasis is the regulated reabsorption of calcium along the nephron. To this end, parathyroid hormone (PTH) is released from the parathyroid gland in response to lowered plasma calcium levels. This hormone acts through the PTH 1 receptor along the nephron to increase urinary phosphate excretion and decrease urinary calcium excretion. In the proximal tubule, PTH inhibits phosphate reabsorption by reducing the abundance of sodium phosphate cotransporters in the apical membrane. PTH likely decreases calcium reabsorption from the proximal tubule, by reducing the reabsorption of sodium, an event necessary for the paracellular movement of calcium across this segment. In the thick ascending limb (TAL), PTH increases calcium permeability and may increase the electrical driving force thereby increasing calcium reabsorption in the TAL. Finally, in the distal convolution, PTH acts to increase transcellular calcium reabsorption by increasing the activity and abundance of the apically expressed calcium channel TRPV5.
Topics: Calcium; Parathyroid Hormone; Phosphates; Kidney Tubules; Kidney Tubules, Proximal
PubMed: 36894509
DOI: 10.1111/apha.13959 -
Current Problems in Cardiology Aug 2023Endomyocardial fibrosis (EMF) is an endemic idiopathic cardiomyopathy denoted by restricted and fibrous myocardium and endocardium. Apical fibrosis may cause thickening... (Review)
Review
Endomyocardial fibrosis (EMF) is an endemic idiopathic cardiomyopathy denoted by restricted and fibrous myocardium and endocardium. Apical fibrosis may cause thickening of the myocardium and extend from the ventricular apices through to the valves, thereby, restricting inflow. EMF is a critical condition that is predominant in the young population. However, it may also be associated with older individuals. Identified areas recorded with cases include the under-developed populations, that is, the tropics of Africa- Uganda, Mozambique; South Asia, and South America. Unlike in the preceded years, further studies are currently on focus to completely evaluate this medical condition. Additionally, this review encompasses the complications that arise from EMF as studied and reported from case studies, clinical trials, experiments, and research including heart failure, atrioventricular valves regurgitations, arrhythmias, serous cavities effusions, circulatory shock, stroke, myocardial ischemic syndromes, hepatic, and end-organ dysfunctions. Complications like heart failure may be very fatal to its victims. Moreover, left ventricular thrombosis may probably impose systemic or cerebral thromboembolism, which would risk the probability of a stroke. All in all, suggestions in the management strategies that have proved effective and advances in cardiac transplantation and of recently proposed therapeutic targets equally take part of this review and may form a foundation to diminishing the remaining inch of EMF and its outcomes.
Topics: Humans; Endomyocardial Fibrosis; Myocardium; Heart Failure; Heart Ventricles; Thrombosis
PubMed: 37003449
DOI: 10.1016/j.cpcardiol.2023.101730