Molecules and Cells最新文献

{"title":"The disordered effector RipAO of Ralstonia solanacearum destabilizes microtubule networks in Nicotiana benthamiana cells","authors":"Hyelim Jeon ,&nbsp;Wanhui Kim ,&nbsp;Cécile Segonzac","doi":"10.1016/j.mocell.2024.100167","DOIUrl":"10.1016/j.mocell.2024.100167","url":null,"abstract":"<div><div><em>Ralstonia solanacearum</em> causes bacterial wilt, a devastating disease in solanaceous crops. The pathogenicity of <em>R. solanacearum</em> depends on its type III secretion system, which delivers a suite of type III effectors into plant cells. The disordered core effector RipAO is conserved across <em>R. solanacearum</em> species and affects plant immune responses when transiently expressed in <em>Nicotiana benthamiana</em>. Specifically, RipAO impairs pathogen-associated molecular pattern–triggered reactive oxygen species production, an essential plant defense mechanism. RipAO fused to yellow fluorescent protein initially localizes to filamentous structures, resembling the cytoskeleton, before forming large punctate aggregates around the nucleus. Consistent with these findings, tubulin alpha 6 (TUA6) and tubulin beta-1, building blocks of microtubules, were identified as putative targets of RipAO in immunoprecipitation and mass spectrometry analyses. In the presence of RipAO, TUA6-labeled microtubules fragmented into puncta, mimicking the effects of oryzalin, a microtubule polymerization inhibitor. These effects were corroborated in a <em>N. benthamiana</em> transgenic line constitutively expressing green fluorescent protein-labeled TUA6, where RipAO reduced microtubule density and stability at an accumulation level that did not induce aggregation. Moreover, oryzalin treatment further enhanced RipAO’s impairment of reactive oxygen species production, suggesting that RipAO disrupts microtubule networks via its association with tubulins, leading to immune suppression. Further research into RipAO’s interaction with the microtubule network will enhance our understanding of bacterial strategies to subvert plant immunity.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"48 1","pages":"Article 100167"},"PeriodicalIF":3.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792086","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":"STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma","authors":"Dongkwan Yoo,&nbsp;Sichen Wu,&nbsp;Seunghyuk Choi,&nbsp;Sung-Oh Huh,&nbsp;Ali Sadra","doi":"10.1016/j.mocell.2024.100145","DOIUrl":"10.1016/j.mocell.2024.100145","url":null,"abstract":"<div><div>miR-454-3p has been reported to be a tumor-suppressive microRNA (miRNA) in multiple cancer types. We identified the kinase STK33 mRNA, which is a high-risk factor for survival in neuroblastoma (NB) patients, as being a substrate of miR-454-3p in NB. Even though STK33 is an attractive target for several cancers, the development of inhibitors of STK33 has been challenging. For the various cell lines tested, we demonstrated reduced growth and viability with the miR-454-3p mimic. From among the candidate NB-associated miRNAs, miR-454-3p mimic and its antagonist had the most profound effect on STK33 mRNA and protein-level changes. Under various conditions of growth and external stress for the cells, the RNA levels for miR-454-3p and STK33 also negatively correlated. Luciferase reporter assays demonstrated STK33 as a substrate for miR-454-3p, and recombinant versions of STK33 resistant to miR-454-3p significantly blunted the suppressive effect of the miR-454-3p and established STK33 as the major functional substrate of miR-454-3p. Overexpression of miR-454-3p or knockdown of STK33 mRNA promoted autophagy and at the same time, increased the apoptotic markers in the tested NB cells, indicating a mechanism for the suppressive effect of the agents. Given the difficult-to-drug targets such as STK33 and the recent successes in RNA delivery methods for cancer treatment, it is thought that targeting cancer cells with a suppressive miRNA such as miR-454-3p for STK33-dependent cancer types may be an alternative means of NB therapy.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100145"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624113","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":"Single-molecule FRET–based approach for protein-targeted drug discovery","authors":"Yuyoung Kim ,&nbsp;Surim Kim ,&nbsp;Kang Heo ,&nbsp;Sanghwa Lee","doi":"10.1016/j.mocell.2024.100150","DOIUrl":"10.1016/j.mocell.2024.100150","url":null,"abstract":"<div><div>Many therapeutic drugs target various proteins involved in diverse biological processes. Among these proteins, type II topoisomerases are critical targets for anticancer and antibacterial chemotherapies, yet the action mechanisms of many type II topoisomerase-targeting drugs have not been fully elucidated. In this regard, the development of rapid and accurate methods to identify the mode of action of potential drug candidates is crucial to improve the efficiency of drug screening and discovery. Here, using type II topoisomerase as a model system, we present a single-molecule fluorescence resonance energy transfer–based drug screening method capable of delineating when and how the drug candidates participate in the entire reaction steps of the target protein. This unique capability has been demonstrated to be applicable to the identification of representative types of widely prescribed drugs targeting type II topoisomerase: etoposide which stabilizes the enzyme-DNA cleavage complex, and bisdioxopiperazines (ICRF-I93) which lock the N-terminal gate of the enzyme into the closed state. Based on this demonstration experiment, we expect that our proposed method will be extended to broad applications in the screening of potent drugs targeting various proteins.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100150"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644400","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":"Dipeptidyl peptidase 4 as an injury-responsive protein in the mouse sciatic nerve","authors":"Yeonsoo Oh,&nbsp;Yongcheol Cho","doi":"10.1016/j.mocell.2024.100159","DOIUrl":"10.1016/j.mocell.2024.100159","url":null,"abstract":"<div><div>Dipeptidyl peptidase 4 (DPP4) is a membrane-bound protease known for its roles in immunity and metabolism; however, its function in the nervous system remains largely unexplored. We found that DPP4 is predominantly expressed in the Schwann cells of the sciatic nerve, and its systemic depletion in postnatal mice resulted in a decline in motor function. Importantly, the inhibition of its proteolytic activity did not affect axon regeneration, indicating that DPP4′s protease activity may not be directly involved in axon regeneration. Instead, we observed a reduction in DPP4 protein levels in the sciatic nerve after injury and increased in serum postinjury, suggesting that DPP4 may be shed into circulation, potentially mediating systemic responses following injury. These findings highlight DPP4′s importance in sensory function and its potential role in systemic responses after peripheral nerve injury.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100159"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693230","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":"Nα-terminal acetylation meets ferroptosis via N-degron pathway","authors":"Jihye Yang ,&nbsp;Cheol-Sang Hwang","doi":"10.1016/j.mocell.2024.100160","DOIUrl":"10.1016/j.mocell.2024.100160","url":null,"abstract":"","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100160"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693287","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":"PKA regulates autophagy through lipolysis during fasting","authors":"Yul Ji ,&nbsp;Yong Geun Jeon ,&nbsp;Won Taek Lee ,&nbsp;Ji Seul Han ,&nbsp;Kyung Cheul Shin ,&nbsp;Jin Young Huh ,&nbsp;Jae Bum Kim","doi":"10.1016/j.mocell.2024.100149","DOIUrl":"10.1016/j.mocell.2024.100149","url":null,"abstract":"<div><div>Autophagy is a crucial intracellular degradation process that provides energy and supports nutrient deprivation adaptation. However, the mechanisms by which these cells detect lipid scarcity and regulate autophagy are poorly understood. In this study, we demonstrate that protein kinase A (PKA)-dependent lipolysis delays autophagy initiation during short-term nutrient deprivation by inhibiting AMP-activated protein kinase (AMPK). Using coherent anti-Stokes Raman spectroscopy, we visualized free fatty acids (FFAs) in vivo and observed that lipolysis-derived FFAs were used before the onset of autophagy. Our data suggest that autophagy is triggered when the supply of FFAs is insufficient to meet energy demands. Furthermore, PKA activation promotes lipolysis and suppresses AMPK-driven autophagy during early fasting. Disruption of this regulatory axis impairs motility and reduces the lifespan of <em>Caenorhabditis elegans</em> during fasting. These findings establish PKA as a critical regulator of catabolic pathways, prioritizing lipolysis over autophagy by modulating AMPK activity to prevent premature autophagic degradation during transient nutrient deprivation.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100149"},"PeriodicalIF":3.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639337","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":"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}