Molecules and Cells最新文献

{"title":"An RXLR effector disrupts vesicle trafficking at ER-Golgi interface for Phytophthora capsici pathogenicity","authors":"Jihyun Kim ,&nbsp;Jesse Kaleku ,&nbsp;Haeun Kim ,&nbsp;Minji Kang ,&nbsp;Hui Jeong Kang ,&nbsp;Jongchan Woo ,&nbsp;Hongshi Jin ,&nbsp;Seungmee Jung ,&nbsp;Cécile Segonzac ,&nbsp;Eunsook Park ,&nbsp;Doil Choi","doi":"10.1016/j.mocell.2024.100158","DOIUrl":"10.1016/j.mocell.2024.100158","url":null,"abstract":"<div><div><em>Phytophthora</em> species, an oomycete plant pathogen, secrete effectors into plant cells throughout their life cycle for manipulating host immunity to achieve successful colonization. However, the molecular mechanisms underlying effector-triggered necrotic cell death remain elusive. In this study, we identified an RXLR (amino acid residue; Arginine-Any amino acid-Leucine-Arginine motif) effector (Pc12) from <em>Phytophthora capsici</em>, which contributes to virulence and induces necrosis by triggering a distinct endoplasmic reticulum (ER) stress response through its interaction with Rab13-2. The necrotic cell death induced by Pc12 did not exhibit conventional effector-triggered immunity-mediated hypersensitive cell death, including the involvement of nucleotide-binding site leucine-rich repeat downstream signaling components and transcriptional reprogramming of defense-related genes. Instead, it alters the localization of ER-resident proteins and confines secretory proteins within the ER. Pc12 directly interacts with Rab13-2, which is primarily localized to the ER and Golgi apparatus, resulting in a diminished Rab13-2 signal on the Golgi apparatus. Furthermore, Rab13-2 exhibits increased affinity for its interactor, Rab escort protein 1, in the presence of Pc12. Structural predictions revealed that a specific residue of Rab13-2 is crucial for binding to the C-terminus of Pc12. Substitution of this residue reduced its interaction with Pc12 and impaired <em>P. capsici</em> infection while maintaining its interaction with Rab escort protein 1 and prenylated Rab acceptor 1. These findings provide insight into how a pathogen effector induces a distinct form of necrotic cell death to facilitate colonization of the host plant by disrupting the recycling of Rab13-2, a protein involved in vesicle trafficking at the ER-Golgi interface.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100158"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(24)00194-8","DOIUrl":"10.1016/S1016-8478(24)00194-8","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100169"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E2F3a activates Gadd45b gene expression through PPARα-mediated transcriptional regulation in hepatic cells","authors":"Min Seok Woo ,&nbsp;Atif Ali Khan Khalil ,&nbsp;Frank J. Gonzalez ,&nbsp;Jung-Hwan Kim","doi":"10.1016/j.mocell.2024.100148","DOIUrl":"10.1016/j.mocell.2024.100148","url":null,"abstract":"<div><div>Growth arrest and DNA damage-inducible beta (GADD45b) plays a critical role in intracellular events such as cell growth and apoptosis. Although the functional study of GADD45b has been conducted, the mechanism for the transcriptional regulation of GADD45b is largely unknown. Due to the drastic induction of hepatic GADD45b mRNA by peroxisome proliferator-activated receptor alpha activation in wild-type mice, we investigated a key factor that affects the upregulation of GADD45b mRNA. Interestingly, we found that GADD45b-promoter luciferase activity was dramatically increased as the 5′-flanking regions were closer to the transcription start site in Hepa1c1c7 cells. Additionally, we found 2 E2F (E2F-myc activator/cell cycle regulator) binding motifs in the region (−150/−1) of the GADD45b promoter. Notably, E2F3 mRNA was significantly increased only in wild-type mice treated with WY-14643, a peroxisome proliferator-activated receptor alpha agonist, followed by the induction of GADD45b mRNA. Furthermore, gene functional studies and Chromatin Immunoprecipitation assays revealed that E2F3 could regulate the GADD45b gene via the E2F binding motif. Thus, we suggest that E2F3 may play a key role in regulating the GADD45b gene as a positive transcription factor.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100148"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of extracellular vesicles from mesenchymal stem cells in regeneration","authors":"Hyeseong Jung ,&nbsp;Yuyeon Jung ,&nbsp;Junsik Seo ,&nbsp;Yeongju Bae ,&nbsp;Han-Soo Kim ,&nbsp;Wooyoung Jeong","doi":"10.1016/j.mocell.2024.100151","DOIUrl":"10.1016/j.mocell.2024.100151","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) are highly valued in regenerative medicine due to their ability to self-renew and differentiate into various cell types. Their therapeutic benefits are primarily due to their paracrine effects, in particular through extracellular vesicles (EVs), which are related to intercellular communication. Recent advances in EV production and extraction technologies highlight the potential of MSC-derived EVs (MSC-EVs) in tissue engineering and regenerative medicine. MSC-EVs offer several advantages over traditional cell therapies, including reduced toxicity and immunogenicity compared with whole MSCs. EVs carrying functional molecules such as growth factors, cytokines, and miRNAs play beneficial roles in tissue repair, fibrosis treatment, and scar prevention by promoting angiogenesis, skin cell migration, proliferation, extracellular matrix remodeling, and reducing inflammation. Despite the potential of MSC-EVs, there are several limitations to their use, including variability in quality, the need for standardized methods, low yield, and concerns about the composition of EVs and the potential risks. Overall, MSC-EVs are a promising alternative to cell-based therapies, and ongoing studies aim to understand their actions and optimize their use for better clinical outcomes in wound healing and skin regeneration.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100151"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board Members/Copyright","authors":"","doi":"10.1016/S1016-8478(24)00196-1","DOIUrl":"10.1016/S1016-8478(24)00196-1","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100171"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143161088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplexed multimodal single-cell technologies: From observation to perturbation analysis","authors":"Su-Hyeon Lee ,&nbsp;Junha Park ,&nbsp;Byungjin Hwang","doi":"10.1016/j.mocell.2024.100147","DOIUrl":"10.1016/j.mocell.2024.100147","url":null,"abstract":"<div><div>Single-cell technologies have undergone a significant transformation, expanding from their initial focus on transcriptomics to encompass a diverse range of modalities. Recent advancements have markedly improved scalability and reduced costs, facilitating the processing of larger cell populations and broadening the scope of single-cell research. The incorporation of clustered regularly interspaced short palindromic repeats (CRISPR)-based perturbations has revolutionized the field by enabling precise functional genomics and detailed studies of gene regulation at the single-cell level. Despite these advancements, challenges persist, particularly in achieving genome-wide perturbations and managing the complexity of high-throughput data. This review discusses the technological milestones that have driven these changes, the current limitations of single-cell CRISPR technologies, and the future directions needed to address these challenges and advance our understanding of cellular biology.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100147"},"PeriodicalIF":3.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontitis and atherosclerotic cardiovascular disease","authors":"June Yeon Kim,&nbsp;Kyeongho Lee,&nbsp;Moon Geon Lee,&nbsp;Sung-Jin Kim","doi":"10.1016/j.mocell.2024.100146","DOIUrl":"10.1016/j.mocell.2024.100146","url":null,"abstract":"<div><div>Atherosclerotic cardiovascular disease (ASCVD) is a major global health concern linked to significant morbidity and mortality. Recent research has explored the relationship between ASCVD and periodontitis, a prevalent inflammatory oral condition. Epidemiological studies have suggested a strong association between periodontitis and ASCVD, even proposing that periodontal disease could be a modifiable risk factor for cardiovascular conditions. This review critically analyzes the current evidence for a potential causal role for periodontitis in ASCVD. While randomized controlled trials have demonstrated reductions in surrogate markers of cardiovascular risk following periodontal interventions, these studies remain inconclusive regarding their direct effects on cardiovascular events. Preclinical studies in animal models have suggested a potential causal relationship between periodontitis and ASCVD, proposing several biological mechanisms to explain this connection. These studies, however, are limited in their ability to definitively prove causality. The positive associations observed in epidemiological studies between periodontitis and ASCVD may also be influenced by various biases, such as confounding and collider stratification. Moreover, our systematic review of Mendelian randomization studies on the causal relationship between periodontitis and ASCVD found no evidence of a genetic causality, further challenging the causal hypothesis. This review underscores the need for further high-quality research clarifying the relationship between periodontitis and ASCVD to better guide clinical practice and public health policy.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100146"},"PeriodicalIF":3.7,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMEM175 plays a crucial role in osteoblast differentiation by regulating lysosomal function and autophagy","authors":"Seung Hye Lee,&nbsp;Ji Sun Jang,&nbsp;Shenzheng Mo,&nbsp;Hong-Hee Kim","doi":"10.1016/j.mocell.2024.100127","DOIUrl":"10.1016/j.mocell.2024.100127","url":null,"abstract":"<div><div>Bone provides structural support, enables movement, protects internal organs, regulates calcium and phosphorus levels, and contains bone marrow essential for hematopoiesis. Osteoblasts are specialized cells responsible for bone formation through the secretion of extracellular matrix components. Transmembrane protein 175 (TMEM175), which functions as an endosomal/lysosomal K⁺ channel and a lysosomal H⁺ channel, regulates lysosomal function and autophagy. Despite the recognized importance of lysosomes and autophagy in osteoblast differentiation, the specific role of TMEM175 in osteoblast differentiation has not been revealed. In this study, we investigated whether TMEM175 is associated with human bone mineral density and fracture and examined the role of TMEM175 in osteoblast differentiation. In analyses of single nucleotide polymorphisms of pore ion channel genes using the mouse2human database, a significant correlation between TMEM175 single nucleotide polymorphisms and human bone mineral density and fracture was identified. TMEM175 expression levels were found to increase during osteoblast differentiation from bone chip-derived mesenchymal stem cells (BMSCs). Knockdown of TMEM175 in BMSCs suppressed osteoblast differentiation, as evidenced by decreased matrix mineralization and lower expression levels of osteoblast marker genes. Further analysis indicated that TMEM175 deficiency leads to lysosomal dysfunction and partially impairs autophagic clearance during osteoblast differentiation. Moreover, the TMEM175 inhibitor 4-aminopyridine decreased osteoblast differentiation of BMSCs. Taken together, this study reveals that TMEM175 plays an important role in osteoblast differentiation by regulating lysosomal function and autophagic clearance.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100127"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover and caption","authors":"","doi":"10.1016/S1016-8478(24)00178-X","DOIUrl":"10.1016/S1016-8478(24)00178-X","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100153"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board Members/Copyright","authors":"","doi":"10.1016/S1016-8478(24)00179-1","DOIUrl":"10.1016/S1016-8478(24)00179-1","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100154"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142704438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}