Yeeun Choi, Eun-Seon Yoo, Youjin Oh, Jong-Woo Sohn
{"title":"Cellular and metabolic function of GIRK1 potassium channels expressed by arcuate POMC and NPY/AgRP neurons","authors":"Yeeun Choi, Eun-Seon Yoo, Youjin Oh, Jong-Woo Sohn","doi":"10.1016/j.mocell.2024.100122","DOIUrl":"10.1016/j.mocell.2024.100122","url":null,"abstract":"<div><div>It is well known that the G protein-gated inwardly rectifying K<sup>+</sup> (GIRK) channels are critical to maintain excitability of central neurons. GIRK channels consist of 4 subunits and GIRK1/GIRK2 heterotetramers are considered to be the neuronal prototype. We previously reported the metabolic significance of GIRK2 subunits expressed by the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARH). However, the role of GIRK1 subunits expressed by the neurons of ARH remains to be determined. In this study, we delineated the contribution of GIRK1 channel subunits to the excitability of the pro-opiomelanocortin (POMC) and NPY/AgRP neurons of the ARH. We further assessed the metabolic function of GIRK1 subunits expressed by these neurons. Our results provide insight into how GIRK channels regulate arcuate POMC and NPY/AgRP neurons and shape metabolic phenotypes.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100122"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142391898","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":"A brief guide to analyzing expression quantitative trait loci","authors":"Byung Su Ko , Sung Bae Lee , Tae-Kyung Kim","doi":"10.1016/j.mocell.2024.100139","DOIUrl":"10.1016/j.mocell.2024.100139","url":null,"abstract":"<div><div>Molecular quantitative trait locus (molQTL) mapping has emerged as an important approach for elucidating the functional consequences of genetic variants and unraveling the causal mechanisms underlying diseases or complex traits. However, the variety of analysis tools and sophisticated methodologies available for molQTL studies can be overwhelming for researchers with limited computational expertise. Here, we provide a brief guideline with a curated list of methods and software tools for analyzing expression quantitative trait loci, the most widely studied type of molQTL.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100139"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504290","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":"The emerging role of gut hormones","authors":"Hyeryeong Cho , Jaechul Lim","doi":"10.1016/j.mocell.2024.100126","DOIUrl":"10.1016/j.mocell.2024.100126","url":null,"abstract":"<div><div>The gut is traditionally recognized as the central organ for the digestion and absorption of nutrients, however, it also functions as a significant endocrine organ, secreting a variety of hormones such as glucagon-like peptide 1, serotonin, somatostatin, and glucocorticoids. These gut hormones, produced by specialized intestinal epithelial cells, are crucial not only for digestive processes but also for the regulation of a wide range of physiological functions, including appetite, metabolism, and immune responses. While gut hormones can exert systemic effects, they also play a pivotal role in maintaining local homeostasis within the gut. This review discusses the role of the gut as an endocrine organ, emphasizing the stimuli, the newly discovered functions, and the clinical significance of gut-secreted hormones. Deciphering the emerging role of gut hormones will lead to a better understanding of gut homeostasis, innovative treatments for disorders in the gut, as well as systemic diseases.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100126"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470233","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}
Sung Ho Boo , Min-Kyung Shin , Hongseok Ha , Jae-Sung Woo , Yoon Ki Kim
{"title":"Transcriptome-wide analysis for glucocorticoid receptor-mediated mRNA decay reveals various classes of target transcripts","authors":"Sung Ho Boo , Min-Kyung Shin , Hongseok Ha , Jae-Sung Woo , Yoon Ki Kim","doi":"10.1016/j.mocell.2024.100130","DOIUrl":"10.1016/j.mocell.2024.100130","url":null,"abstract":"<div><div>The glucocorticoid receptor (GR) can bind to DNA or RNA, eliciting transcriptional activation/repression or rapid messenger RNA (mRNA) degradation, respectively. Although GR-mediated transcriptional regulation has been well-characterized, the molecular details of rapid mRNA degradation induced by glucocorticoids are not yet fully understood. Here, we demonstrate that glucocorticoid-induced GR-mediated mRNA decay (GMD) takes place in the nucleus and the cytoplasm, acting on pre-mRNAs and mRNAs. We also performed cross-linking and immunoprecipitation coupled with high-throughput sequencing analysis for GMD factors (GR, YBX1, and HRSP12) and mRNA sequencing analysis to identify endogenous GMD substrates. Our comprehensive coupled with high-throughput sequencing and mRNA sequencing analyses reveal that a range of cellular transcripts containing a common binding site for GR, YBX1, and HRSP12 are preferential targets for GMD, suggesting possible new functions of GMD in various biological events.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100130"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470235","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":"The role of p21 in cellular senescence and aging-related diseases","authors":"Jiayu Yan, Siyi Chen, Zimei Yi, Ruowen Zhao, Jiayu Zhu, Shuwen Ding, Junhua Wu","doi":"10.1016/j.mocell.2024.100113","DOIUrl":"10.1016/j.mocell.2024.100113","url":null,"abstract":"<div><div>During the aging process or disease progression, normal cells and tissues in the body undergo various stresses, leading to cell damage and the need for repair, adaptation, apoptosis, or defense responses. Cellular senescence is a key player in this process, influencing the rate of aging and disease progression. It can be triggered by different stress factors, resulting in irreversible cell cycle arrest and functional decline. Senescent cells often show high expression of cell cycle factors such as p21 and p16, which are involved in cell cycle arrest. p16 has long been recognized as a significant marker of aging. Recent evidence suggests that p21<sup>high</sup> cells and p16<sup>high</sup> cells represent distinct cell populations in terms of cell type, tissue location, accumulation kinetics, and physiological functions. This article focuses on recent advancements in understanding p21-dependent cellular senescence. It starts by providing an overview of the role of p21 in 3 primary cellular senescence phenotypes where it plays a crucial role. It then delves into the pathogenesis of diseases closely linked to p21-dependent cellular senescence, particularly metabolic disorders and cardiovascular diseases. The article also discusses progress in p21-related animal models and outlines strategies for utilizing p21 to intervene in cellular senescence by delaying aging, eliminating senescent cells, and rejuvenating senescent cells. This review systematically examines the pathogenesis of p21-dependent cellular senescence, emphasizing its importance in studying aging heterogeneity and developing new senolytic therapies. It aims to stimulate future research on leveraging p21 to enhance the characteristics of senescent cells, allowing more precise methods for eliminating harmful senescent cells at the right time, thereby delaying aging and potentially achieving rejuvenation.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100113"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291502","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}
Dongju Kim , Mee-Sup Yoon , Junwon Lee , Shin-Young Park , Joong-Soo Han
{"title":"Effects of phospholipase D1-inhibitory peptide on the growth and metastasis of gastric cancer cells","authors":"Dongju Kim , Mee-Sup Yoon , Junwon Lee , Shin-Young Park , Joong-Soo Han","doi":"10.1016/j.mocell.2024.100128","DOIUrl":"10.1016/j.mocell.2024.100128","url":null,"abstract":"<div><div>Phospholipase D1 (PLD1) contributes to cancer development and progression through its effects on cell proliferation, survival, invasion, metastasis, angiogenesis, drug resistance, and modulation of the tumor microenvironment. Its central role in these processes makes it a promising target for novel cancer treatments aimed at inhibiting its activity and disrupting the signaling pathways it regulates. In this study, we aimed to investigate the effect of PLD1 inhibition on gastric cancer cell growth using a novel peptide inhibitor, TAT-TVTSP. PLD1, which plays a role in cancer progression, catalyzes the conversion of phosphatidylcholine into choline and phosphatidic acid through hydrolysis. To effectively target PLD1 in cells, we engineered TAT-TVTSP by fusing a PLD1-inhibitory peptide (TVTSP) with a cell-penetrating peptide (TAT). We observed that TAT-TVTSP effectively inhibited PLD1 activity in AGS gastric cancer cells. Moreover, TAT-TVTSP significantly inhibited the mammalian target of the rapamycin signaling pathway, including the phosphorylation of key downstream targets such as S6K1, AKT, S473, glycogen synthase kinase-3b, and forkhead box O1. TAT-TVTSP did not induce cell death, but it triggered cell cycle arrest by activating p21 and p27 via AKT phosphorylation. Functional assays revealed that TAT-TVTSP significantly impaired the colony-forming ability of AGS cells, thus inhibiting cell proliferation. Transwell and wound-healing assays revealed that this peptide disrupted the cellular behaviors critical to cancer progression, such as migration and invasion. In vivo, TAT-TVTSP significantly reduced tumor growth in the xenograft model of gastric cancer without any toxicity. Overall, our results suggest that TAT-TVTSP is a novel therapeutic agent for PLD1-mediated cancers.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100128"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470229","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}
Taeyeon Hong , Junho Park , Garam An , Jisoo Song , Gwonhwa Song , Whasun Lim
{"title":"Evaluation of organ developmental toxicity of environmental toxicants using zebrafish embryos","authors":"Taeyeon Hong , Junho Park , Garam An , Jisoo Song , Gwonhwa Song , Whasun Lim","doi":"10.1016/j.mocell.2024.100144","DOIUrl":"10.1016/j.mocell.2024.100144","url":null,"abstract":"<div><div>There is increasing global concern about environmental pollutants, such as heavy metals, plastics, pharmaceuticals, personal care products, and pesticides, which have been detected in a variety of environments and are likely to be exposed to nontarget organisms, including humans. Various animal models have been utilized for toxicity assessment, and zebrafish are particularly valuable for studying the toxicity of various compounds owing to their similarity to other aquatic organisms and 70% genetic similarity to humans. Their development is easy to observe, and transgenic models for organs such as the heart, liver, blood vessels, and nervous system enable efficient studies of organ-specific toxicity. This suggests that zebrafish are a valuable tool for evaluating toxicity in specific organs and forecasting the potential impacts on other nontarget species. This review describes organ toxicity caused by various toxic substances and their mechanisms in zebrafish.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100144"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568896","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":"Brief guide to flow cytometry","authors":"Youngkwon Song, Yoontae Lee","doi":"10.1016/j.mocell.2024.100129","DOIUrl":"10.1016/j.mocell.2024.100129","url":null,"abstract":"<div><div>Flow cytometry is a powerful analytical technique for measuring the physical and chemical properties of cells or particles as they flow through a beam of light in a fluid stream. It is widely used in several research fields for a wide variety of purposes. This article provides a concise guide to the principles and utilization of flow cytometry. Step-by-step instructions, from instrument setup to data analysis, are intended to help researchers successfully apply flow cytometry in their studies.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 11","pages":"Article 100129"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470228","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}
Mücahit Varlı , Kyungha Lee , Kyo Bin Kang , Hangun Kim
{"title":"Unveiling the antimetastatic activity of monoterpene indole alkaloids targeting MMP9 in cancer cells, with a focus on pharmacokinetic and cellular insights","authors":"Mücahit Varlı , Kyungha Lee , Kyo Bin Kang , Hangun Kim","doi":"10.1016/j.mocell.2024.100143","DOIUrl":"10.1016/j.mocell.2024.100143","url":null,"abstract":"<div><div>Distant metastasis, together with acquired resistance, limits the therapeutic impact of chemotherapy and molecularly targeted therapies. The properties of the tumor microenvironment determine how sensitive or resistant various cancers are to specific pharmacological treatments. Matrix metalloproteinase 9 (MMP9) is widely known for its ability to break down the extracellular matrix and it also modulates the motility of cancer cells. Here, our goal was to identify compounds that target MMP9 and evaluate their capacity to inhibit the motility of cancer cells. The antimetastatic effect of monoterpene indole alkaloids (MIAs) on cell viability and motility was evaluated by methyl thiazolyl tetrazolium assay, migration assay, invasion assay, quantitative real-time polymerase chain reaction, pathway-focused expression analysis, Western blotting, reporter assay, molecular docking simulation, and target prediction. MIA compounds target MMP9. MIAs inhibited the expression of phospho-epidermal growth factor receptor, phospho-Akt, phospho-JNK, and cyclin D1. Additionally, MIAs had predicted favorable pharmacokinetic profile and drug-like properties. Furthermore, among the MIA compounds, lyaloside and 5(S)-5-carbomethoxystrictosidine had low cytotoxicity and regulated cancer-related signaling, including cell migration, cell invasion, epithelial-mesenchymal transition, and immune evasion. Our findings demonstrated that the MIAs used in this study have potential antimetastasis properties that occur via MMP9-mediated regulation of cancer signaling and have the potential to be used therapeutically at safe doses.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100143"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558275","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}
Na Yeong Lee , Mi-Lang Kyun , Ji Eun Yu , Sun-Ok Kim , Key-Hwan Lim , Kyung Ho Lee
{"title":"Transport of Golgi-localized β-catenin p-S47 by KIF11 or KIFC3 induces primary ciliogenesis","authors":"Na Yeong Lee , Mi-Lang Kyun , Ji Eun Yu , Sun-Ok Kim , Key-Hwan Lim , Kyung Ho Lee","doi":"10.1016/j.mocell.2024.100142","DOIUrl":"10.1016/j.mocell.2024.100142","url":null,"abstract":"<div><div>Primary cilium is an important hub for cell signaling and dysregulation of primary cilia assembly and disassembly is associated with the development of cancer and chemotherapeutic drug resistance, as well as the genetic disorders collectively known as ciliopathy. β-catenin plays a major role in canonical Wnt signaling; however, its association with primary cilia has only recently been highlighted in reports of β-catenin-mediated primary ciliogenesis. In this study, we found that β-catenin p-S47 was localized to the Golgi apparatus and the nucleus, and the amount of β-catenin p-S47 at these locations was significantly higher during primary ciliogenesis compared with asynchronous cell growth conditions. In addition, the novel β-catenin-binding motor proteins KIF11 and KIFC3 were shown to have a lower binding affinity in β-catenin S47A than in β-catenin wild-type. Knockdown of KIF11 or KIFC3 resulted in primary cilia deficiency and increased β-catenin p-S47 levels in the Golgi apparatus and were accompanied by a decrease in β-catenin p-S47 at the centrosome. The accumulation of β-catenin p-S47 in the nucleus was increased during primary ciliogenesis along with β-catenin-dependent transcriptional activity. The collective findings indicate the existence of a novel mechanism of primary ciliogenesis involving KIF11-/KIFC3-associated β-catenin p-S47 in the Golgi apparatus and β-catenin p-S47 transcriptional activity in the nucleus. This study revealed a new mechanism for the study of ciliopathies, cancer, and chemotherapeutic drug resistance caused by primary ciliogenesis dysregulation and provides new targets for drug development to treat these diseases.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"47 12","pages":"Article 100142"},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546432","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}