Cell Chemical Biology最新文献_第10页

A new light on PLCβ! PLCβ 的新亮点！

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.chembiol.2024.06.007

Sithurandi Ubeysinghe , Waruna Thotamune , Ajith Karunarathne

引用次数: 0

Blocking smoothened cholesterylation: A strategy for overcoming drug resistance in cancer 阻断平滑胆固醇化：克服癌症抗药性的策略

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.chembiol.2024.06.005

Steven Y. Cheng , Ying E. Zhang

引用次数: 0

Behavioral control through the direct, focal silencing of neuronal activity 通过直接抑制神经元活动控制行为

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.chembiol.2024.04.003

{"title":"Behavioral control through the direct, focal silencing of neuronal activity","authors":"","doi":"10.1016/j.chembiol.2024.04.003","DOIUrl":"10.1016/j.chembiol.2024.04.003","url":null,"abstract":"<div><p>The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group. Exposing the caged toxin, STX-bpc, to a brief (5 ms) pulse of light effects rapid release of a potent STX derivative and transient, spatially precise blockade of voltage-gated sodium channels (Na<sub>V</sub>s). We demonstrate the efficacy of STX-bpc for parametrically manipulating action potentials in mammalian neurons and brain slice. Additionally, we show the effectiveness of this reagent for silencing neural activity by dissecting sensory-evoked swimming in larval zebrafish. Photo-uncaging of STX-bpc is a straightforward method for non-invasive, reversible, spatiotemporally precise neural silencing without the need for genetic access, thus removing barriers for comparative research.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 7","pages":"Pages 1324-1335.e20"},"PeriodicalIF":6.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624001314/pdfft?md5=44c00102a463b68a137b8af752a2e736&pid=1-s2.0-S2451945624001314-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery of YAP1/TAZ pathway inhibitors through phenotypic screening with potent anti-tumor activity via blockade of Rho-GTPase signaling 通过表型筛选发现 YAP1/TAZ 通路抑制剂，这些抑制剂通过阻断 Rho-GTPase 信号传导具有强大的抗肿瘤活性。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.chembiol.2024.02.013

引用次数: 0

CYP7B1-mediated 25-hydroxycholesterol degradation maintains quiescence-activation balance and improves therapeutic potential of mesenchymal stem cells CYP7B1 介导的 25- 羟基胆固醇降解可维持静止-激活平衡，并提高间充质干细胞的治疗潜力

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.chembiol.2024.01.009

{"title":"CYP7B1-mediated 25-hydroxycholesterol degradation maintains quiescence-activation balance and improves therapeutic potential of mesenchymal stem cells","authors":"","doi":"10.1016/j.chembiol.2024.01.009","DOIUrl":"10.1016/j.chembiol.2024.01.009","url":null,"abstract":"<div><p>Stem cells remain quiescent <em>in vivo</em> and become activated in response to external stimuli. However, the mechanism regulating the quiescence-activation balance of bone-marrow-derived mesenchymal stem cells (BM-MSCs) is still unclear. Herein, we demonstrated that CYP7B1 was the common critical molecule that promoted activation and impeded quiescence of BM-MSCs under inflammatory stimulation. Mechanistically, CYP7B1 degrades 25-hydroxycholesterol (25-HC) into 7α,25-dihydroxycholesterol (7α,25-OHC), which alleviates the quiescence maintenance effect of 25-HC through Notch3 signaling pathway activation. CYP7B1 expression in BM-MSCs was regulated by NF-κB p65 under inflammatory conditions. BM-MSCs from CYP7B1 conditional knockout (CKO) mice had impaired activation abilities, relating to the delayed healing of bone defects. Intravenous infusion of BM-MSCs overexpressing CYP7B1 could improve the pathological scores of mice with collagen-induced arthritis. These results clarified the quiescence-activation regulatory mechanism of BM-MSCs through the NF-κB p65-CYP7B1-Notch3 axis and provided insight into enhancing BM-MSCs biological function as well as the subsequent therapeutic effect.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 7","pages":"Pages 1277-1289.e7"},"PeriodicalIF":6.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400045X/pdfft?md5=2bea7d0b66678d99d585b4f6835df184&pid=1-s2.0-S245194562400045X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139916158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A light-controlled phospholipase C for imaging of lipid dynamics and controlling neural plasticity 用于脂质动态成像和控制神经可塑性的光控磷脂酶 C

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-07-18 DOI: 10.1016/j.chembiol.2024.03.001

{"title":"A light-controlled phospholipase C for imaging of lipid dynamics and controlling neural plasticity","authors":"","doi":"10.1016/j.chembiol.2024.03.001","DOIUrl":"10.1016/j.chembiol.2024.03.001","url":null,"abstract":"<div><p>Phospholipase C (PLC) is a key enzyme that regulates physiological processes via lipid and calcium signaling. Despite advances in protein engineering, no tools are available for direct PLC control. Here, we developed a novel optogenetic tool, light-controlled PLCβ (opto-PLCβ). Opto-PLCβ uses a light-induced dimer module, which directs an engineered PLC to the plasma membrane in a light-dependent manner. Our design includes an autoinhibitory capacity, ensuring stringent control over PLC activity. Opto-PLCβ triggers reversible calcium responses and lipid dynamics in a restricted region, allowing precise spatiotemporal control of PLC signaling. Using our system, we discovered that phospholipase D-mediated phosphatidic acid contributes to diacylglycerol clearance on the plasma membrane. Moreover, we extended its applicability <em>in vivo</em>, demonstrating that opto-PLCβ can enhance amygdala synaptic plasticity and associative fear learning in mice. Thus, opto-PLCβ offers precise spatiotemporal control, enabling comprehensive investigation of PLC-mediated signaling pathways, lipid dynamics, and their physiological consequences <em>in vivo</em>.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 7","pages":"Pages 1336-1348.e7"},"PeriodicalIF":6.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624000904/pdfft?md5=c7d9dcebdd64d13b97a9d4dcb03f6078&pid=1-s2.0-S2451945624000904-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potent and selective binders of the E3 ubiquitin ligase ZNRF3 stimulate Wnt signaling and intestinal organoid growth E3泛素连接酶ZNRF3的强效和选择性结合物刺激Wnt信号传导和肠道类器官生长。

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2023.11.006

Yvonne T. Kschonsak , Xinxin Gao , Stephen E. Miller , Sunhee Hwang , Hadir Marei , Ping Wu , Yanjie Li , Karen Ruiz , Kristel Dorighi , Loryn Holokai , Pirunthan Perampalam , Wen-Ting K. Tsai , Yee-Seir Kee , Nicholas J. Agard , Seth F. Harris , Rami N. Hannoush , Felipe de Sousa e Melo

{"title":"Potent and selective binders of the E3 ubiquitin ligase ZNRF3 stimulate Wnt signaling and intestinal organoid growth","authors":"Yvonne T. Kschonsak , Xinxin Gao , Stephen E. Miller , Sunhee Hwang , Hadir Marei , Ping Wu , Yanjie Li , Karen Ruiz , Kristel Dorighi , Loryn Holokai , Pirunthan Perampalam , Wen-Ting K. Tsai , Yee-Seir Kee , Nicholas J. Agard , Seth F. Harris , Rami N. Hannoush , Felipe de Sousa e Melo","doi":"10.1016/j.chembiol.2023.11.006","DOIUrl":"10.1016/j.chembiol.2023.11.006","url":null,"abstract":"<div><p>Selective and precise activation of signaling transduction cascades is key for cellular reprogramming and tissue regeneration. However, the development of small- or large-molecule agonists for many signaling pathways has remained elusive and is rate limiting to realize the full clinical potential of regenerative medicine. Focusing on the Wnt pathway, here we describe a series of disulfide-constrained peptides (DCPs) that promote Wnt signaling activity by modulating the cell surface levels of ZNRF3, an E3 ubiquitin ligase that controls the abundance of the Wnt receptor complex FZD/LRP at the plasma membrane. Mechanistically, monomeric DCPs induce ZNRF3 ubiquitination, leading to its cell surface clearance, ultimately resulting in FZD stabilization. Furthermore, we engineered multimeric DCPs that induce expansive growth of human intestinal organoids, revealing a dependence between valency and ZNRF3 clearance. Our work highlights a strategy for the development of potent, biologically active Wnt signaling pathway agonists via targeting of ZNRF3.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 6","pages":"Pages 1176-1187.e10"},"PeriodicalIF":6.6,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Induced proximity labeling and editing for epigenetic research 用于表观遗传学研究的诱导近似标记和编辑技术

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.005

Chenwei Zhou , Sarah Wagner , Fu-Sen Liang

引用次数: 0

A double whammy for KEAP1 KEAP1 的双重打击

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.chembiol.2024.05.014

Jan Gerhartz , Radosław P. Nowak

引用次数: 0

Meet the authors: Markella Konstantinidou and Michelle R. Arkin 与作者见面马凯拉-康斯坦丁尼杜和米歇尔-R-阿金