Protein trafficking and maturation regulate intramembrane proteolysis

AbstractIntramembrane-cleaving proteases (I-CLiPs) are membrane embedded proteolytic enzymes. All substrates identified so far are also membrane proteins, involving a number of critical cellular signaling as well as human diseases. After synthesis and assembly at the endoplasmic reticulum, membrane proteins are exported to the Golgi apparatus and transported to their sites of action. A number of studies have revealed the importance of the intracellular membrane trafficking in i-CLiP-mediated intramembrane proteolysis, not only for limiting the unnecessary encounter between i-CLiPs and their substrate but also for their cleavage site preference. In this review, we will discuss recent advances in our understanding of how each i-CLiP proteolysis is regulated by intracellular vesicle trafficking. This article is part of a Special Issue entitled: Intramembrane Proteases

Presenilin-dependent intramembrane cleavage of ephrin-B1

BACKGROUND: Presenilin-dependent γ-secretase cleavage of several transmembrane proteins, including amyloid-β precursor protein and Notch, mediates the intramembrane proteolysis to liberate their intracellular domains that are involved in cellular signaling. Considering γ-secretase inhibitors as therapeutics for Alzheimer's disease, understanding the physiologically and biologically important substrate for γ-secretase activity in brains is emerging issue. To elucidate the molecular mechanism and physiological role of γ-secretase, we screened candidate molecules for γ-secretase substrates. RESULTS: We show that ephrin-B1, that participates in cell-cell repulsive and attractive signaling together with its Eph receptor, constitutively undergoes ectodomain shedding and that the residual membrane-tethered fragment is sequentially cleaved by γ-secretase to release the intracellular domain. Furthermore, overexpression of membrane-tethered ephrin-B1 caused protrusion of numerous cellular processes consisted of F-actin, that required the preservation of the most C-terminal region of ephrin-B1. In contrast, soluble intracellular domain translocated into the nucleus and had no effect on cell morphology. CONCLUSION: Our findings suggest that ephrin-B is a genuine substrate for γ-secretase and regulates the cytoskeletal dynamics through intramembrane proteolysis

Development of Water Gridded Ion Thruster for Small Satellites: Toward On-Orbit Demonstration

Water as a propellant has many advantages and does not require a pressure vessel for storage. Its high safety level can reduce development cost and time. It is also a resource tightly tied to human spaceflight and found in-situ in the upcoming moon missions. Stored in its liquid state in our thrusters, it is then vaporized at room temperature and low pressure. The resulted steam is then injected in the discharge chambers where it is transformed into plasma. Plasma generation is achieved through flight-proven microwave discharge using Electron Cyclotron Resonance

GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation

AbstractWe identified two novel GATA2 mutations in acute myeloid leukemia (AML). One mutation (p.R308P-GATA2) was a R308P substitution within the zinc finger (ZF)-1 domain, and the other (p.A350_N351ins8-GATA2) was an eight-amino-acid insertion between A350 and N351 residues within the ZF-2 domain. p.R308P-GATA2 did not affect DNA-binding and transcriptional activities, while p.A350_N351ins8-GATA2 reduced them, and impaired G-CSF-induced granulocytic differentiation of 32D cells. Although p.A350_N351ins8-GATA2 did not show a dominant-negative effect over wild-type (Wt)–GATA2 by the reporter assay, it might be involved in the pathophysiology of AML by impairing myeloid differentiation because of little Wt-GATA2 expression in primary AML cells harboring the p.A350_N351ins8 mutation

High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors

<p>Abstract</p> <p>Background</p> <p>High glucose can induce apoptosis in vascular endothelial cells, which may contribute to the development of vascular complications in diabetes. We evaluated the role of the death receptor pathway of apoptotic signaling in high glucose-induced apoptosis in human coronary artery endothelial cells (HCAECs).</p> <p>Methods</p> <p>HCAECs were treated with media containing 5.6, 11.1, and 16.7 mM of glucose for 24 h in the presence or absence of tumor necrosis factor (TNF)-α. For detection of apoptosis, DNA fragmentation assay was used. HCAEC expression of death receptors were analyzed by the PCR and flow cytometry methods. Also, using immunohistochemical techniques, coronary expression of death receptors was assessed in streptozotocin-nicotinamide-induced type 2 diabetic mice.</p> <p>Results</p> <p>Exposure of HCAECs to high glucose resulted in a significant increase in TNF-R1 and Fas expression, compared with normal glucose. High glucose increased TNF-α production by HCAECs and exogenous TNF-α up-regulated TNF-R1 and Fas expression in HCAECs. High glucose-induced up-regulation of TNF-R1 and Fas expression was undetectable in the presence of TNF-α. Treatment with TNF-R1 neutralizing peptides significantly inhibited high glucose-induced endothelial cell apoptosis. Type 2 diabetic mice displayed appreciable expression of TNF-R1 and Fas in coronary vessels.</p> <p>Conclusions</p> <p>In association with increased TNF-α levels, the death receptors, TNF-R1 and Fas, are up-regulated in HCAECs under high glucose conditions, which could in turn play a role in high glucose-induced endothelial cell apoptosis.</p

シオミズツボワムシの増殖、両性生殖誘導及びサイズに与えるDMSO、NaOH、アセトン、エタノール添加の影響

Dimethyl sulfoxide (DMSO), sodium hydroxide (NaOH), acetone, and ethanol which are commonly used as solvents for steroid and thyroid hormones were tested for their effect on rotifer population growth, mictic female production, and body size. Each chemical was tested at 0.2%, 0.4%, 0.6%, 0.8% and 1% of the 5-ml Nannochloropsis oculata suspension (7×10⁶cells/ml). Initially, 5 rotifers each carrying one amictic egg were exposed in these concentrations at 25℃ in dark condition for 48 hours. Thereafter, rotifers were counted and transferred to a new culture medium without the chemical on day 2, 4, 6, and 8. Body size was measured on day 8. DMSO at 0.2% and 0.4% significantly increased rotifer population growth while 0.4, 0.6, 0.8, and 1% caused an increase in mictic female production. NaOH at 0.4% and 0.8% significantly increased population growth while 0.8% caused an increase in mictic female production. Acetone at 0.8% and 1% caused a decrease in population growth but it had no effect on mictic female production. Ethanol caused a decrease in population growth in all tested concentrations but it did not affect mictic female production. Body size of DMSO-, NaOH-, acetone-, or ethanol-treated rotifers was not significantly different from that of the control. Acetone may be used as a solvent at concentrations lower than 0.8.%, whereas DMSO and NaOH may be used as high as 1% without adverse effects. Ethanol caused adverse effects as low as 0.2% and is therefore not suitable as solvent in experiments with rotifer populations.不溶性のステロイドホルモンや重金属化合物等の溶剤として用いられる,ジメチルスルホオキシド,水酸化ナトリウム,アセトン,エチルアルコール(ワムシ培養への添加濃度は各々0.2, 0.6, 0.8, 1.0%)が,ワムシの生殖特性とサイズにどのような影響を与えるか検討した。0.2%および0.4%DMSOの添加によってワムシの増殖は促進され,一方0.4%以上の濃度では両性生殖誘導率が高くなった。NaOHを0.4, 0.8%添加するとワムシ増殖率は高くなった。エタノールの添加はいずれの濃度でもワムシの増殖を阻害したが,0.6%以下のアセトン添加ではワムシの生殖特性に対する影響はみられなかった。いずれの溶剤もワムシのサイズに影響を与えることはなかった。以上の結果はワムシのホルモン作用や毒性評価試験の生物材料としてワムシを使用する場合の基礎知見となるものである

X-ray study of ferroic octupole order producing anomalous Hall effect

放射光でついに見えた磁気オクタポール --熱を電気に変える新たな担い手--. 京都大学プレスリリース. 2021-09-27.Recently found anomalous Hall, Nernst, magnetooptical Kerr, and spin Hall effects in the antiferromagnets Mn₃X (X = Sn, Ge) are attracting much attention for spintronics and energy harvesting. Since these materials are antiferromagnets, the origin of these functionalities is expected to be different from that of conventional ferromagnets. Here, we report the observation of ferroic order of magnetic octupole in Mn₃Sn by X-ray magnetic circular dichroism, which is only predicted theoretically so far. The observed signals are clearly decoupled with the behaviors of uniform magnetization, indicating that the present X-ray magnetic circular dichroism is not arising from the conventional magnetization. We have found that the appearance of this anomalous signal coincides with the time reversal symmetry broken cluster magnetic octupole order. Our study demonstrates that the exotic material functionalities are closely related to the multipole order, which can produce unconventional cross correlation functionalities