Plant-specific tail-anchored coiled-coil protein MAG3 stabilizes Golgi-associated ERESs to facilitate protein exit from the ER

Endoplasmic reticulum exit sites (ERESs) are ER subdomains where coat protein complex II carriers are assembled for ER-to-Golgi transport. We previously proposed a dynamic capture-and-release model of ERESs by Golgi stacks in plants. However, how ERESs and Golgi stacks maintain a stable interaction in plant cells with vigorous cytoplasmic streaming is unknown. Here, we show that a plant-specific ER transmembrane protein, which we designate as MAG3, plays a crucial role in mediating the capture-and-release of ERESs in Arabidopsis. We isolated a mutant (mag3) defective in protein exit from the ER in seeds. MAG3 localized specifically to the ER-Golgi interface with Golgi-associated ERESs and remained there after ERES release. MAG3 deficiency caused a reduction in the amount of ERESs associated with each Golgi stack. MAG3 interacted with WPP DOMAIN PROTEINs, which are also plant-specific. These results suggest that plants have evolved a unique system to support ER-to-Golgi transport despite intracellular motility

Sucrose starvation induces microautophagy in plant root cells

Abstract Autophagy is an essential system for degrading and recycling cellular components for survival during starvation conditions. Under sucrose starvation, application of a papain protease inhibitor E-64d to the Arabidopsis root and tobacco BY-2 cells induced the accumulation of vesicles, labeled with a fluorescent membrane marker FM4-64. The E-64d-induced vesicle accumulation was reduced in the mutant defective in autophagy-related genes ATG2, ATG5, and ATG7, suggesting autophagy is involved in the formation of these vesicles. To clarify the formation of these vesicles in detail, we monitored time-dependent changes of tonoplast, and vesicle accumulation in sucrose-starved cells. We found that these vesicles were derived from the tonoplast and produced by microautophagic process. The tonoplast proteins were excluded from the vesicles, suggesting that the vesicles are generated from specific membrane domains. Concanamycin A treatment in GFP-ATG8a transgenic plants showed that not all FM4-64-labeled vesicles, which were derived from the tonoplast, contained the ATG8a-containing structure. These results suggest that ATG8a may not always be necessary for microautophagy.This study was supported by the National Science Centre, Poland [UMO-2016/21/P/NZ9/01089 to SG-Y (the project has received funding from the European Union's Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 665778) and UMO-2016/23/B/NZ1/01847 to KeY]; the Foundation for Polish Science (TEAM/2017-4/41 to KeY); KAKENHI from the Japan Society for the Promotion of Science, Japan (JP15J40032 to SG-Y, JP17K07457 to SM, and JP15H05776 to IH-N); and KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology, Japan (JP26111523 to SG-Y); as well as the institutional support provided from the National Institute for Basic Biology (NIBB), Kyoto University, and Małopolska Centre of Biotechnology, Jagiellonian University. Next-generation sequencing was supported by NIBB Collaborative Research Programs 11-711

Elevated Serum Immunoglobulin G1 Levels and Left Ventricular Diastolic Dysfunction in Anti-Centromere Antibody–Positive Patients With Lower Extremity Arterial Disease: A Cross-Sectional Study

Shiraki T., Kioka H., Ueda-Hayakawa I., et al. Elevated Serum Immunoglobulin G1 Levels and Left Ventricular Diastolic Dysfunction in Anti-Centromere Antibody–Positive Patients With Lower Extremity Arterial Disease: A Cross-Sectional Study. Journal of Dermatology 52(6), 1070-1077 (2025); https://doi.org/10.1111/1346-8138.17783.This cross-sectional pilot study investigated the clinical characteristics of anti-centromere antibody (ACA)–positive patients with below-the-knee arterial disease. Sixteen ACA-positive patients (mean age 69 ± 10 years; 94% women) underwent contrast-enhanced computed tomography evaluation, with arterial damage scored using the Global Limb Anatomic Staging System. Lower extremity arterial disease (LEAD) was defined as a below-the-knee arterial score ≥ 1 or > 50% stenosis in above-the-knee lesions. Eight patients were categorized into the LEAD group (below-the-knee arterial damage score 12 ± 6). The LEAD group showed significantly higher serum IgG1 levels (1029 ± 484 vs. 531 ± 72 mg/dL, p < 0.001) and a higher prevalence of diastolic dysfunction (62% vs. 0%, p = 0.026) compared to the non-LEAD group. Patients with diastolic dysfunction had significantly higher serum IgG1 levels than those without (1190 ± 559 vs. 593 ± 139 mg/dL, p = 0.008). These findings suggest associations between elevated serum IgG1 levels, below-the-knee arterial disease, and left ventricular diastolic dysfunction in ACA-positive patients

Pexophagy suppresses ROS-induced damage in leaf cells under high-intensity light

Although light is essential for photosynthesis, it has the potential to elevate intracellular levels of reactive oxygen species (ROS). Since high ROS levels are cytotoxic, plants must alleviate such damage. However, the cellular mechanism underlying ROS-induced leaf damage alleviation in peroxisomes was not fully explored. Here, we show that autophagy plays a pivotal role in the selective removal of ROS-generating peroxisomes, which protects plants from oxidative damage during photosynthesis. We present evidence that autophagy-deficient mutants show light intensity-dependent leaf damage and excess aggregation of ROS-accumulating peroxisomes. The peroxisome aggregates are specifically engulfed by pre-autophagosomal structures and vacuolar membranes in both leaf cells and isolated vacuoles, but they are not degraded in mutants. ATG18a-GFP and GFP-2×FYVE, which bind to phosphatidylinositol 3-phosphate, preferentially target the peroxisomal membranes and pre-autophagosomal structures near peroxisomes in ROS-accumulating cells under high-intensity light. Our findings provide deeper insights into the plant stress response caused by light irradiation

Safety and feasibility of adjuvant chemotherapy with S-1 in Japanese breast cancer patients after primary systemic chemotherapy: a feasibility study

BACKGROUND: Advanced breast cancer patients have a higher risk of postoperative recurrence than early-stage breast cancer patients. Recurrence is believed to be caused by the increase in micrometases, which were not eradicated by preoperative or postoperative chemotherapy. Therefore, a new therapeutic strategy that can improve treatment efficacy is mandatory for advanced breast cancer. S-1 was shown to be effective and safe in Japanese metastatic breast cancer patients treated with previous chemotherapy, including anthracyclines. Thus, in this study, we evaluated S-1 as adjuvant chemotherapy in breast cancer patients after standard primary systemic chemotherapy. METHODS: The treatment consisted of 18 courses (a 2-week administration and a 1-week withdrawal; one year) administered at 80–120 mg/body/day. In cases judged to require postoperative radiotherapy, it was concurrently initiated on Day 1 of the study. If the estrogen receptor and/or human epidermal growth factor receptor 2 were positive, endocrine therapy and/or trastuzumab were permitted, concurrently. RESULTS: Of the 45 patients enrolled between September 2007 and September 2009 from 3 institutions, 43 patients were eligible. Thirty-two of the 43 (74.4%) patients received concurrent radiotherapy. Twenty-two of the 43 (51.2%) patients completed the scheduled courses of chemotherapy. The most common reasons for withdrawal of treatment were subjective symptoms, such as nausea, anorexia, or general fatigue during the first 9 courses of treatment in 9/43 (20.9%) patients, recurrence in 7/43 (16.3%) patients, and adverse events in 5/43 (11.6%) patients. The cumulative percentage of administration for 365 days was 66.4% (95% confidence interval: 50.8–79.1%). Although grade 3 neutropenia (9.3%), leukopenia (4.7%), and diarrhea (4.7%) were observed, they were manageable. No grade 4 adverse effects were observed. CONCLUSIONS: The percentage of Japanese breast cancer patients completing the 18-course treatment and the cumulative percentage of administration for 365 days using S-1 after standard primary systemic chemotherapy were similar with the results of another study of adjuvant chemotherapy for the Japanese gastric cancer patients with no severe adverse effects. A phase III trial investigating the usefulness of adjuvant S-1 is now ongoing in Japan, and it is expected that S-1 will have a significant survival benefit in breast cancer patients. UMIN000013469

Regulation of organ straightening and plant posture by an actin–myosin XI cytoskeleton

植物の姿勢を決めるしくみの解明 -まっすぐになろうとする力-. 京都大学プレスリリース. 2015-04-07.Plants are able to bend nearly every organ in response to environmental stimuli such as gravity and light. After this first phase, the responses to stimuli are restrained by an independent mechanism, or even reversed, so that the organ will stop bending and attain its desired posture. This phenomenon of organ straightening has been called autotropism and autostraightening and modelled as proprioception. However, the machinery that drives organ straightening and where it occurs are mostly unknown. Here, we show that the straightening of inflorescence stems is regulated by an actin–myosin XI cytoskeleton in specialized immature fibre cells that are parallel to the stem and encircle it in a thin band. Arabidopsis mutants defective in myosin XI (specifically XIf and XIk) or ACTIN8 exhibit hyperbending of stems in response to gravity, an effect independent of the physical properties of the shoots. The actin–myosin XI cytoskeleton enables organs to attain their new position more rapidly than would an oscillating series of diminishing overshoots in environmental stimuli. We propose that the long actin filaments in elongating fibre cells act as a bending tensile sensor to perceive the organ's posture and trigger the straightening system