•Endosome organization function, biogenesis and differences across species are discussed.•Endosomes form two membrane networks connected by multivesicular transport intermediates.•The early endosome: ...main sorting station that controls membrane flow along recycling and degradation pathways.•The late endosome: central hub for incoming traffic and outgoing traffic and a key sensing/signaling platform.
Efficient sorting of the material internalized by endocytosis is essential for key cellular functions and represents a, if not the, major trafficking pathway in mammalian cells. Incoming material – solutes, receptors and cargos, lipids and even pathogenic agents – are routed to various destinations within mammalian cells at two major sorting stations: the early and late endosome. The early endosome receives all manner of incoming material from the plasma membrane, as well as from the Golgi, and serves as an initial sorting nexus routing molecules back to the cell surface through recycling endosomes, to the trans-Golgi network by retrograde transport, or on to the late endosome/lysosome. The early endosome also regulates cell signaling, through the downregulation of internalized receptors, which are packaged into intralumenal vesicles that arise from inward invaginations of the limiting membrane. These multivesicular regions detach or mature from early endosomes and become free endocytic carrier vesicle/multivesicular body, which transports cargoes to late endosomes. The late endosome provides a central hub for incoming traffic from the endocytic, biosynthetic and autophagic pathways and outgoing traffic to the lysosomes, the Golgi complex or the plasma membrane. They also function as a key sensing/signaling platform that inform the cell about the nutrient situation. Herein we summarize the current understanding of the organization and functions of the endocytic pathway, differences across species, and the process of endosome maturation.
The ionic nature of endosomes varies considerably in character along the endocytic pathway. Counter‐ion flux across the limiting membrane of endosomes has long been considered essential for full ...acidification and normal endosome/lysosomal function. The proximal functions of luminal ions, however, have been difficult to assess. The recent development of transgenic mice carrying mutations in the intracellular chloride channels (ClCs) has provided a tool to uncouple Cl− influx from endosomal acidification. Intriguingly, many of the defects of the endo‐lysomal system attributed to aberrant pH persist in the Cl−‐deficient mice implying a direct regulatory role for Cl− influx in endosome function. These observations may begin to explain the abundance of endosomal ion transporters, including ClCs, sodium‐proton exchangers, two‐pore channels and mucolipins, that have been localized to endo‐lysosomes, and the extensive changes in luminal ion composition therein. In this review, we summarize what is known regarding the mediators of endosomal ion flux, and discuss the implications of changing ionic content on endo‐lysosomal function.
The ionic nature of endosomes varies considerably in character along the endocytic pathway. Counter-ion flux across the limiting membrane of endosomes has long been considered essential for full ...acidification and normal endosome/lysosomal function. The proximal functions of luminal ions, however, have been difficult to assess. The recent development of transgenic mice carrying mutations in the intracellular chloride channels (ClCs) has provided a tool to uncouple Cl⁻ influx from endosomal acidification. Intriguingly, many of the defects of the endo-lysomal system attributed to aberrant pH persist in the Cl⁻-deficient mice implying a direct regulatory role for Cl⁻ influx in endosome function. These observations may begin to explain the abundance of endosomal ion transporters, including ClCs, sodium-proton exchangers, two-pore channels and mucolipins, that have been localized to endo-lysosomes, and the extensive changes in luminal ion composition therein. In this review, we summarize what is known regarding the mediators of endosomal ion flux, and discuss the implications of changing ionic content on endo-lysosomal function.
Powdery mildew on cannabis (Cannabis sativa L., marijuana), caused by Golovinomyces cichoracearum, reduces plant growth and overall quality. To investigate disease management options, biological, ...chemical and physical approaches were assessed. A mildew-susceptible strain, 'Copenhagen Kush', was grown indoors with continual exposure to mildew inoculum. Treatments were applied weekly over a four-week period to groups of four plants once mildew infection had established itself. Trials were repeated thrice under varying initial disease pressures. Disease assessments were made weekly and the percentage of area infected on 30 leaflets per plant was used to calculate a disease rating score for treated and control plants. Disease progress curves were plotted and AUDPC values were determined for each treatment. To test the effect of UV-C light on mildew development, plants were exposed daily for 3-5 s over 28 days to UV-C light. The response of 12 cannabis strains to powdery mildew infection was assessed after exposing them to inoculum over a period of two weeks. The most effective treatments that significantly (P < 0.05) reduced disease in three trials were Luna Privilege SC (fluopyram), Regalia
®
Maxx, MilStop
®
, Rhapsody ASO
TM
, neem oil, and Stargus
®
. Treatments that were less effective included ZeroTol
®
, boric acid, and Actinovate
®
SP. Daily exposure of plants to UV-C light significantly reduced disease (by 45.2%, P < 0.05). Seven of 12 cannabis strains had significantly lower disease severity compared with the other five strains. The disease management strategies evaluated in this study have potential for reducing powdery mildew development on cannabis.
A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide. Severe acute ...respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein. Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences. This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.
Platelets are small, anucleate entities that bud from megakaryocytes in the bone marrow. Among circulating cells, platelets are the most abundant cell, traditionally involved in regulating the ...balance between thrombosis (the terminal event of platelet activation) and hemostasis (a protective response to tissue injury). Although platelets lack the precise cellular control offered by nucleate cells, they are in fact very dynamic cells, enriched in preformed RNA that allows them the capability of de novo protein synthesis which alters the platelet phenotype and responses in physiological and pathological events. Antiplatelet medications have significantly reduced the morbidity and mortality for patients afflicted with thrombotic diseases, including stroke and myocardial infarction. However, it has become apparent in the last few years that platelets play a critical role beyond thrombosis and hemostasis. For example, platelet-derived proteins by constitutive and regulated exocytosis can be found in the plasma and may educate distant tissue including blood vessels. First, platelets are enriched in inflammatory and anti-inflammatory molecules that may regulate vascular remodeling. Second, platelet-derived microparticles released into the circulation can be acquired by vascular endothelial cells through the process of endocytosis. Third, platelets are highly enriched in mitochondria that may contribute to the local reactive oxygen species pool and remodel phospholipids in the plasma membrane of blood vessels. Lastly, platelets are enriched in proteins and phosphoproteins which can be secreted independent of stimulation by surface receptor agonists in conditions of disturbed blood flow. This so-called biomechanical platelet activation occurs in regions of pathologically narrowed (atherosclerotic) or dilated (aneurysmal) vessels. Emerging evidence suggests platelets may regulate the process of angiogenesis and blood flow to tumors as well as education of distant organs for the purposes of allograft health following transplantation. This review will illustrate the potential of platelets to remodel blood vessels in various diseases with a focus on the aforementioned mechanisms.
Macropinocytosis is differentiated from other types of endocytosis by its unique susceptibility to inhibitors of Na⁺/H⁺ exchange. Yet, the functional relationship between Na⁺/H⁺ exchange and ...macropinosome formation remains obscure. In A431 cells, stimulation by EGF simultaneously activated macropinocytosis and Na⁺/H⁺ exchange, elevating cytosolic pH and stimulating Na⁺ influx. Remarkably, although inhibition of Na⁺/H⁺ exchange by amiloride or HOE-694 obliterated macropinocytosis, neither cytosolic alkalinization nor Na⁺ influx were required. Instead, using novel probes of submembranous pH, we detected the accumulation of metabolically generated acid at sites of macropinocytosis, an effect counteracted by Na⁺/H⁺ exchange and greatly magnified when amiloride or HOE-694 were present. The acidification observed in the presence of the inhibitors did not alter receptor engagement or phosphorylation, nor did it significantly depress phosphatidylinositol-3-kinase stimulation. However, activation of the GTPases that promote actin remodelling was found to be exquisitely sensitive to the submembranous pH. This sensitivity confers to macropinocytosis its unique susceptibility to inhibitors of Na⁺/H⁺ exchange.
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