MYO1C stabilizes actin and facilitates the arrival of transport carriers at the Golgi complex

In this study, we aimed to identify the myosin motor proteins that control trafficking at the Golgi complex. In addition to the known Golgi-associated myosins MYO6, MYO18A and MYH9 (myosin IIA), we identified MYO1C as a novel player at the Golgi in a human cell line. We demonstrate that depletion of MYO1C induces Golgi complex fragmentation and decompaction. MYO1C accumulates at dynamic structures around the Golgi complex that colocalize with Golgi-associated actin dots. MYO1C depletion leads to loss of cellular F-actin, and Golgi complex decompaction is also observed after inhibition or loss of the actin-related protein 2/3 complex, Arp2/3 (also known as ARPC). We show that the functional consequence of MYO1C depletion is a delay in the arrival of incoming transport carriers, both from the anterograde and retrograde routes. We propose that MYO1C stabilizes actin at the Golgi complex, facilitating the arrival of incoming transport carriers at the Golgi.This article has an associated First Person interview with the first author of the paper.Fil: Capmany, Anahi. Institute Curie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Inmunologia; ArgentinaFil: Yoshimura, Azumi. Institute Curie; FranciaFil: Kerdous, Rachid. Institute Curie; FranciaFil: Caorsi, Valentina. Abbelight; FranciaFil: Lescure, Aurianne. Institute Curie; FranciaFil: Nery, Elaine Del. Institute Curie; FranciaFil: Coudrier, Evelyne. Institute Curie; FranciaFil: Goud, Bruno. Institute Curie; FranciaFil: Schauer, Kristine. Institute Curie; Franci

Synergistic action of dendritic mitochondria and creatine kinase maintains ATP homeostasis and actin dynamics in growing neuronal dendrites.

発達中の脳で神経細胞内のエネルギーを維持するしくみを解明. 京都大学プレスリリース. 2015-04-16.The distribution of mitochondria within mature, differentiated neurons is clearly adapted to their regional physiological needs and can be perturbed under various pathological conditions, but the function of mitochondria in developing neurons has been less well studied. We have studied mitochondrial distribution within developing mouse cerebellar Purkinje cells and have found that active delivery of mitochondria into their dendrites is a prerequisite for proper dendritic outgrowth. Even when mitochondria in the Purkinje cell bodies are functioning normally, interrupting the transport of mitochondria into their dendrites severely disturbs dendritic growth. Additionally, we find that the growth of atrophic dendrites lacking mitochondria can be rescued by activating ATP-phosphocreatine exchange mediated by creatine kinase (CK). Conversely, inhibiting cytosolic CKs decreases dendritic ATP levels and also disrupts dendrite development. Mechanistically, this energy depletion appears to perturb normal actin dynamics and enhance the aggregation of cofilin within growing dendrites, reminiscent of what occurs in neurons overexpressing the dephosphorylated form of cofilin. These results suggest that local ATP synthesis by dendritic mitochondria and ATP-phosphocreatine exchange act synergistically to sustain the cytoskeletal dynamics necessary for dendritic development

Sucrose Solution Ingestion Exacerbates Dinitrofluorobenzene-Induced Allergic Contact Dermatitis in Rats

Allergic dermatitis is a skin disease with growing prevalence worldwide that has been associated with diets high in fats and sugars. Regular consumption of sucrose-containing beverages may increase the risk for several health problems, including allergic diseases and particularly asthma, but the association between sucrose consumption and allergic dermatitis is understudied. We investigated the effects of sucrose solution intake on allergic contact dermatitis in rats and found early exacerbation of 2,4-dinitrofluorobenzene (DNFB)-induced disease symptoms and altered composition of the gut microbiota after 14 d of intake. The levels of short-chain fatty acids—produced by fermentation by the intestinal microbiota—were not affected in the cecal contents and feces but decreased in the blood; this effect was especially notable for acetate. To restore blood acetate concentrations, triacetin was mixed with a 10% sucrose solution and fed to the rat model. This strategy prevented the early exacerbation of DNFB-induced symptoms. The decreased absorption of short-chain fatty acids from the intestinal lumen was not linked to the decreased expression of short-chain fatty acid transporters in the small intestine; instead, the mechanism involves a reduction in the sodium concentration in the intestinal lumen due to increased expression of sodium–glucose transporter 1 (SGLT1)

Branched Actin Maintains Acetylated Microtubule Network in the Early Secretory Pathway

In the early secretory pathway, the delivery of anterograde cargoes from the endoplasmic reticulum (ER) exit sites (ERES) to the Golgi apparatus is a multi-step transport process occurring via the ER-Golgi intermediate compartment (IC, also called ERGIC). While the role microtubules in ER-to-Golgi transport has been well established, how the actin cytoskeleton contributes to this process remains poorly understood. Here, we report that Arp2/3 inhibition affects the network of acetylated microtubules around the Golgi and induces the accumulation of unusually long RAB1/GM130-positive carriers around the centrosome. These long carriers are less prone to reach the Golgi apparatus, and arrival of anterograde cargoes to the Golgi is decreased upon Arp2/3 inhibition. Our data suggest that Arp2/3-dependent actin polymerization maintains a stable network of acetylated microtubules, which ensures efficient cargo trafficking at the late stage of ER to Golgi transport

A 3D Sphere Culture System Containing Functional Polymers for Large-Scale Human Pluripotent Stem Cell Production

ヒト多能性幹細胞(ES/iPS細胞)の新たな三次元培養法 -大量培養・大規模生産を可能に-. 京都大学プレスリリース. 2014-04-25.Utilizing human pluripotent stem cells (hPSCs) in cell-based therapy and drug discovery requires large-scale cell production. However, scaling up conventional adherent cultures presents challenges of maintaining a uniform high quality at low cost. In this regard, suspension cultures are a viable alternative, because they are scalable and do not require adhesion surfaces. 3D culture systems such as bioreactors can be exploited for large-scale production. However, the limitations of current suspension culture methods include spontaneous fusion between cell aggregates and suboptimal passaging methods by dissociation and reaggregation. 3D culture systems that dynamically stir carrier beads or cell aggregates should be refined to reduce shearing forces that damage hPSCs. Here, we report a simple 3D sphere culture system that incorporates mechanical passaging and functional polymers. This setup resolves major problems associated with suspension culture methods and dynamic stirring systems and may be optimal for applications involving large-scale hPSC production

Stenting for subclavian steal phenomenon to restore cerebral perfusion due to acute carotid occlusion following carotid endarterectomy: a case report

Abstract Background Perioperative symptomatic carotid artery occlusion after carotid endarterectomy is a rare complication. In this study, we present a case of symptomatic acute carotid artery occlusion that occurred after carotid endarterectomy in a patient with coexistent subclavian artery steal phenomenon, which was successfully treated with subclavian artery stenting. Case presentation A 57-year-old East Asian female presented with stenosis in the left common carotid artery and left subclavian artery along with subclavian steal. The proximal segment of the left anterior cerebral artery was hypoplastic, and the posterior communicating arteries on both sides were well-developed. Left internal carotid artery stenosis progressed during the follow-up examination; therefore, left carotid endarterectomy was performed. On the following day, symptoms of cerebral perfusion deficiency appeared due to occlusion of the left carotid artery. The stenotic origin of the left common carotid artery and the suspected massive thrombus in the left carotid artery posed challenges to carotid revascularization. Therefore, left subclavian artery stenting for the subclavian steal phenomenon was determined to be the best option for restoring cerebral blood flow to the whole brain. Her symptoms improved after the procedure, and the postprocedural workup revealed improved cerebral blood flow. Conclusion Subclavian artery stenting is safe and may be helpful in patients with cerebral perfusion deficiency caused by intractable acute carotid occlusion coexisting with the subclavian steal phenomenon. Revascularization of asymptomatic subclavian artery stenosis is generally not recommended. However, cerebral circulatory insufficiency as a comorbidity may be worth considering

Perspective on the response of marine calcifiers to global warming and ocean acidification—Behavior of corals and foraminifera in a high CO2 world “hot house”

Abstract The CO2 concentration of air has increased over the last two centuries and recently surpassed 400 ppm. Carbon cycle models project CO2 concentrations of 720 to 1000 ppm for the IPCC intermediate scenario (RCP 6.0), resulting in an increase in global mean temperature of ~ 2.6 °C and a decrease in seawater pH of ~ 0.3. Together, global warming and ocean acidification are often referred to as the “evil twins” of climate change, potentially inducing severe threats in the near future. In this paper, our discussion is focused on the response of two major calcifiers, foraminifera and corals, which contribute much to the global carbonate burial rate. Photosymbiosis is regarded as an adaptive ecology for living in warm and oligotrophic oceans, especially for reef-building corals and larger reef-dwelling benthic foraminifera. As a consequence of global warming, bleaching may be a global threat to algal symbiont-bearing marine calcifying organisms under conditions of high temperature and light intensity. If CO2 is dissolved in seawater, the partial pressure of CO2 in seawater (pCO2) and dissolved inorganic carbon (DIC) increases while pH and the saturation state of carbonate minerals decreases without any change in total alkalinity. Generally, marine calcifying organisms show decreases in calcification rates in response to acidified seawater. However, the response often differs depending on situations, species, and life-cycle stage. Some benthic foraminifera showed a positive response to low pH conditions. The Acropora digitifera coral calcification of adult branches was not reduced markedly at higher pCO2 conditions, although calcification tended to decrease versus pCO2 in both aposymbiotic and symbiotic polyps. New analytical technologies help identify important constraints on calcification processes. Based upon Ca isotopes, the transport path of Ca2+ and the degree of its activity would predominantly control the carbonate precipitation rate. Visualization of the extracellular pH distribution shows that proton pumping produces the high internal pH and large internal–external pH gap in association with foraminiferal calcification. From the perspective of a long-term change in the Earth’s surface environment, foraminifera seem to be more adaptive and robust than corals in coping with ocean warming and acidification but it is necessary to further understand the mechanisms underlying variations in sensitivity to heat stress and acidified seawater for future prediction. Since CO2 is more soluble in lower temperature seawater, ocean acidification is more critical in the polar and high-latitude regions. Additionally, older deep-water has enhanced acidity owing to the addition of CO2 from the degradation of organic matter via a synergistic effect with high pressure. With current ocean acidification, pH and the saturation state of carbonate minerals are decreasing without any change in total alkalinity. However, in the Earth’s history, it is well known that alkalinity has fluctuated significantly. Therefore, it is necessary to quantitatively reconstruct alkalinity, which is another key factor determining the saturation state of carbonate minerals. The rapid release of anthropogenic CO2 (in the present day and at the Paleocene/Eocene boundary) induces severe ocean acidification, whereas in the Cretaceous, slow environmental change, even at high levels of pCO2, could raise alkalinity, thereby neutralizing ocean acidification