Article
|
Open Access
Featured
-
-
Article
| Open Access
Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers
The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Here, the authors show that EGFR lung cancer mutations promote the assembly of kinase-active dimers within ligand-free EGFR oligomers. These dimers bind ligand with high affinity and promote tumor growth.
- R. Sumanth Iyer
- , Sarah R. Needham
- & Marisa L. Martin-Fernandez
-
Article
| Open Access
Hepatic nutrient and hormone signaling to mTORC1 instructs the postnatal metabolic zonation of the liver
The liver is segregated into spatially organized areas that serve distinct functions, though how these zones are patterned remains unclear. Here they show that mTORC1 controls spatial segregation of liver metabolic functions via modulation of Wnt signaling, and find that impaired zonation is also observed in pigs given total parenteral nutrition.
- Ana Belén Plata-Gómez
- , Lucía de Prado-Rivas
- & Alejo Efeyan
-
Article
| Open Access
Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage
Hepatocytes regenerate the liver after injury, however, the tissue repair mechanisms have been little explored. Here, the authors show that midlobular and pericentral hepatocytes increase their number and size in response to chemical, physical, and viral insults facilitating liver regeneration.
- Inmaculada Ruz-Maldonado
- , John T. Gonzalez
- & Carlos Fernández-Hernando
-
Article
| Open Access
Mammalian cell growth characterisation by a non-invasive plate reader assay
Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here the authors develop a high throughput non-invasive method for tracking suspension and adhesion mammalian cell growth based on plate reader measures to characterize engineered cell lines.
- Alice Grob
- , Chiara Enrico Bena
- & Francesca Ceroni
-
Article
| Open Access
VWCE modulates amino acid-dependent mTOR signaling and coordinates with KICSTOR to recruit GATOR1 to the lysosomes
mTORC1 adapts cellular metabolism in response to nutrient signals. Here, the authors identify VWCE as a negative regulator of amino acid-dependent mTORC1 signaling and a potential as a therapeutic target in prostate cancer treatments.
- Tianyu Zhao
- , Yuanyuan Guan
- & Ying Liu
-
Article
| Open Access
Acetyl-CoA is a key molecule for nephron progenitor cell pool maintenance
Cell metabolism plays pivotal roles during kidney embryogenesis. This research shows that glycolysis modulation affects nephron progenitor cells via Acetyl-CoA-modulated pathways, influencing both kidney development, and nephron endowment at birth.
- Fabiola Diniz
- , Nguyen Yen Nhi Ngo
- & Giovane G. Tortelote
-
Article
| Open Access
Maintenance of appropriate size scaling of the C. elegans pharynx by YAP-1
Imbalance in the growth rate of two organs can perturb their appropriate scaling. Here, Stojanovski et al., identify a mechanism involving the mechanotransducer YAP-1 which ensures proper proportions of the pharynx and the body length of C. elegans.
- Klement Stojanovski
- , Ioana Gheorghe
- & Benjamin D. Towbin
-
Article
| Open Access
Two subtypes of GTPase-activating proteins coordinate tip growth and cell size regulation in Physcomitrium patens
Using the moss Physcomitrium patens, the authors reveal that PpRopGAPs and PpRenGAP redundantly regulate tip growth by inactivating ROP GTPases and influencing their membrane organization. They display distinct GAP activities and binding capacities to ROPs and oppositely regulate cell width when overexpressed.
- Jingtong Ruan
- , Linyu Lai
- & Peishan Yi
-
Article
| Open Access
Hierarchical organization and assembly of the archaeal cell sheath from an amyloid-like protein
Cellular cryoET reveals how an amyloid-like protein of the prototypical archaeon, Methanospirillum hungatei, oligomerizes into a ring containing a giant 2700-strand β sheet, and how rings stack into hoops and into the cylindrical sheath of the cell.
- Hui Wang
- , Jiayan Zhang
- & Z. Hong Zhou
-
Article
| Open Access
IGF1R-phosphorylated PYCR1 facilitates ELK4 transcriptional activity and sustains tumor growth under hypoxia
Additional roles of metabolic enzymes in cancer remain to be explored. Here, the authors show nuclear localized PYCR1 undergoes IGF1R-mediated phosphorylation under hypoxia, binds with ELK4 and recruits SIRT7 to modulate transcription of target genes to promote colorectal cancer progression.
- Ke Zheng
- , Nannan Sha
- & Tao Chen
-
Article
| Open Access
Whole-genome screens reveal regulators of differentiation state and context-dependent migration in human neutrophils
Neutrophils provide a critical early defense as part of our innate immune system. Here, authors performed a genome-wide assessment of the molecular factors critical to proliferation, differentiation, and cell migration in a neutrophil-like cell.
- Nathan M. Belliveau
- , Matthew J. Footer
- & Julie A. Theriot
-
Article
| Open Access
Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization
Cystinosis is a lysosomal storage disease that affects the kidney. Here, the authors use preclinical models and advanced profiling techniques to discover the mechanism by which defective cystine mobilization from lysosomes disrupts kidney cell function, offering insights into potential therapies.
- Marine Berquez
- , Zhiyong Chen
- & Alessandro Luciani
-
Article
| Open Access
Cancer lineage-specific regulation of YAP responsive elements revealed through large-scale functional epigenomic screens
YAP activation is a key driver in both malignant pleural mesothelioma and uveal melanoma through engagement of different regulatory elements. Here, the authors use functional epigenomic analyses to reveal lineage-specific YAP-dependent cistrome.
- Inês A. M. Barbosa
- , Rajaraman Gopalakrishnan
- & Giorgio G. Galli
-
Article
| Open Access
Endothelial FAT1 inhibits angiogenesis by controlling YAP/TAZ protein degradation via E3 ligase MIB2
The authors report that endothelial protocadherin FAT1 inhibits endothelial proliferation and angiogenesis by promoting degradation of the transcriptional cofactors YAP and TAZ by direct interaction with the E3 ubiquitin ligase Mind Bomb-2 (MIB2).
- Rui Li
- , Jingchen Shao
- & Stefan Offermanns
-
Article
| Open Access
Growth anisotropy of the extracellular matrix shapes a developing organ
Tissue morphogenesis is a complex process that involves tissue growth, mechanics, and shape changes. This work demonstrates that differences in growth rate and direction between a tissue layer and its associated extracellular matrix drive 3D shape changes during organ growth.
- Stefan Harmansa
- , Alexander Erlich
- & Thomas Lecuit
-
Article
| Open Access
Peptidoglycan recycling mediated by an ABC transporter in the plant pathogen Agrobacterium tumefaciens
Some bacteria use the muropeptide transporter AmpG for uptake and recycling of cell wall fragments that are released during cell growth and division. Here, Gilmore & Cava show that the plant pathogen Agrobacterium tumefaciens, which lacks an AmpG homologue, uses a different type of transporter for the same function, which is essential for normal growth in this organism.
- Michael C. Gilmore
- & Felipe Cava
-
Article
| Open Access
IL6 supports long-term expansion of hepatocytes in vitro
Hepatocytes are very difficult to expand in vitro. Here the authors discover that IL6 promotes long-term expansion (>30 passages) of primary mouse hepatocytes in vitro by converting the cells into hepatic progenitor cells, which maintain full capacity of differentiation into hepatocytes.
- Ren Guo
- , Mengmeng Jiang
- & Xin Xie
-
Article
| Open Access
Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist
The authors previously identified a family of viral insulin-like peptides (VILPs) with high homology to human insulin/IGF−1. Here, they report that one of these VILPs exhibits antagonist properties associated with a unique conformation of the IGF1R.
- Francois Moreau
- , Nicholas S. Kirk
- & C. Ronald Kahn
-
Article
| Open Access
The Hippo pathway links adipocyte plasticity to adipose tissue fibrosis
Adipose tissue fibrosis is connected to obesity-related metabolic dysfunction. Qiu and colleagues discover that the Hippo pathway acts as a molecular switch in the initiation and development of adipose tissue fibrosis upon TGFβ stimulation.
- Hongyu Shen
- , Xun Huang
- & Yifu Qiu
-
Article
| Open Access
A Dilp8-dependent time window ensures tissue size adjustment in Drosophila
Mechanisms ensuring developmental precision are poorly understood. Here Blanco-Obregon et al. report reciprocal feedback between Dilp8 and Ecdysone, two hormones required during a precise time window of Drosophila development for organ size adjustment.
- D. Blanco-Obregon
- , K. El Marzkioui
- & L. Boulan
-
Article
| Open Access
Structural basis for assembly and disassembly of the IGF/IGFBP/ALS ternary complex
Insulin-like growth factor 1 (IGF1) regulates growth and differentiation. Here, authors report the atomic structure of the ternary complex (IGF1/IGF-binding protein3/acid labile subunit) and its assembly/disassembly mechanism for IGF bioavailability.
- Hyojin Kim
- , Yaoyao Fu
- & Ho Min Kim
-
Article
| Open Access
High-resolution mass measurements of single budding yeast reveal linear growth segments
Measuring the mass of individual microbial cells remains challenging. Here, the authors present a cell balance to monitor the proliferation of single budding yeast cells under culture conditions in real time, showing that single cells increase total mass in multiple linear segments of constant growth rates.
- Andreas P. Cuny
- , K. Tanuj Sapra
- & Daniel J. Müller
-
Article
| Open Access
Molecular basis of mEAK7-mediated human V-ATPase regulation
Structural basis of V-ATPase regulation by endogenous proteins is unclear. Here, the authors find mEAK7 as an endogenous V-ATPase modulator and determine its structure with V-ATPase, suggesting the potential role of mEAK7 in V-ATPase regulation.
- Rong Wang
- , Yu Qin
- & Xiaochun Li
-
Article
| Open Access
Coupling of growth rate and developmental tempo reduces body size heterogeneity in C. elegans
Animals must reach the correct size during development, despite stochastic differences in their growth rate. Here, Stojanovski et al. show that a coupling of growth and development by an oscillatory timer buffers fluctuations in the growth of the nematode C. elegans to ensure its correct size.
- Klement Stojanovski
- , Helge Großhans
- & Benjamin D. Towbin
-
Article
| Open Access
YAP inhibits ERα and ER+ breast cancer growth by disrupting a TEAD-ERα signaling axis
Recent studies have reported that oncoprotein YAP can function as tumour suppressor in certain contexts. Here the authors show that inhibition of Hippo signalling or YAP activation blocks ERα transcriptional program and ER + breast cancer growth and mechanistically this is through YAP interfering with TEAD-ERα signalling axis.
- Xu Li
- , Shu Zhuo
- & Jin Jiang
-
Article
| Open Access
Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways
Pan-cancer proteomics analysis enables the analysis of protein expression across multiple cancer types. Here, the authors compare proteomics from 14 cancer types and show 11 distinct subtypes across multiple cancer types. Proteome data could link higher pathway activity levels with somatic alteration of specific genes in the pathway.
- Yiqun Zhang
- , Fengju Chen
- & Chad J. Creighton
-
Article
| Open Access
Quantitative phosphoproteomic analyses identify STK11IP as a lysosome-specific substrate of mTORC1 that regulates lysosomal acidification
mTORC1, central regulator of cell growth and autophagy suppressor, is activated on the lysosome surface, but its local role in lysosomal biology remains unclear. Here the authors show STK11IP is a substrate of mTORC1 that regulates lysosomal acidification through V-ATPase and represses autophagy.
- Zhenzhen Zi
- , Zhuzhen Zhang
- & Yonghao Yu
-
Article
| Open Access
Transcriptional repression of estrogen receptor alpha by YAP reveals the Hippo pathway as therapeutic target for ER+ breast cancer
Hippo signalling is reported to be required for proper ESR1 expression. Here the authors reveal that the transcriptional repression of ESR1 is via LATS-YAP-TEAD-VGLL3 axis and the epigenetic regulation of ESR1 super enhancer in ER + breast cancer.
- Shenghong Ma
- , Tracy Tang
- & Kun-Liang Guan
-
Article
| Open Access
Cell adhesion molecule KIRREL1 is a feedback regulator of Hippo signaling recruiting SAV1 to cell-cell contact sites
How cell-cell contact is sensed by Hippo pathway is poorly understood. Here, the authors show that KIRREL1 functions as a feedback regulator of the mammalian Hippo pathway by sensing cell-cell interaction and recruiting SAV1 to cell-cell contacts.
- Atanu Paul
- , Stefano Annunziato
- & Feng Cong
-
Article
| Open Access
EpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis
Maturing erythroblasts become smaller with every cell division. Here, the authors show that Epo stimulation promotes cell division and also generates larger red cells, and that this occurs in mouse and human cells, suggesting that red cell size could be a diagnostic marker for hypoxic stress.
- Daniel Hidalgo
- , Jacob Bejder
- & Merav Socolovsky
-
Article
| Open Access
Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals
Hox genes are highly conserved and well-known for their role in segmental patterning during early development. Here, the authors identify an unreported role for Hox genes in the adult tissue patterning and fission behavior required for asexual reproduction in planarian flatworms.
- Christopher P. Arnold
- , Analí Migueles Lozano
- & Alejandro Sánchez Alvarado
-
Article
| Open Access
The impact of physiological metabolite levels on serine uptake, synthesis and utilization in cancer cells
Cancer cells in culture are often grown in media conditions containing unphysiological metabolite levels. Here, the authors grow cells under physiological metabolite levels to further understand the reliance of cells on serine and find that when grown under these conditions the cells are less sensitive to serine withdrawal.
- Marc Hennequart
- , Christiaan F. Labuschagne
- & Karen H. Vousden
-
Article
| Open Access
USP11 controls R-loops by regulating senataxin proteostasis
DNA:RNA hybrids (R-loops) are products of transcription that impact genome integrity and gene expression. Here the authors reveal a mechanism for regulating R-loops in a ubiquitination-dependent manner controlled by the activities of USP11 and KEAP1
- Mateusz Jurga
- , Arwa A. Abugable
- & Sherif F. El-Khamisy
-
Article
| Open Access
Application of 3D MAPs pipeline identifies the morphological sequence chondrocytes undergo and the regulatory role of GDF5 in this process
Inability to image large numbers of growth plate chondrocytes while retaining their spatial context during analysis has hindered the study of bone development. Here, the authors present a pipeline called 3D MAPs and use it to uncover morphogenic behaviors and growth strategies in normal bones as well as aberrations in Gdf5 KO bones.
- Sarah Rubin
- , Ankit Agrawal
- & Elazar Zelzer
-
Article
| Open Access
The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis
Genomic amplification of chromosome 3q often encodes proteins that contribute to cancer development. Here the authors identify a non-coding product of the 3q region, the lncRNA PLANE that promotes tumorigenesis through the deregulation of transcriptional corepressor NCOR2 pre-mRNA splicing.
- Liu Teng
- , Yu Chen Feng
- & Xu Dong Zhang
-
Article
| Open Access
Probing bacterial cell wall growth by tracing wall-anchored protein complexes
Dynamic cell wall assembly is key to cell shape maintenance during bacterial growth. Here, the authors present a method that allows high-resolution analysis of active and inert zones of cell wall growth during bacterial elongation. They also formulate a mathematical model to predict the partitioning of cell wall-anchored proteins following cell division.
- Yi-Jen Sun
- , Fan Bai
- & Chien-Jung Lo
-
Article
| Open Access
Precise regulation of the relative rates of surface area and volume synthesis in bacterial cells growing in dynamic environments
Bacterial cells actively change their size and shape in response to external environments. Here, Shi et al. explore how cells regulate their morphology during rapid environmental changes, showing that the characteristic dynamics of surface area-to-volume ratio are conserved across genetic and chemical perturbations, as well as across species and growth temperatures.
- Handuo Shi
- , Yan Hu
- & Kerwyn Casey Huang
-
Article
| Open Access
SARS-CoV-2 infection rewires host cell metabolism and is potentially susceptible to mTORC1 inhibition
The pandemic of COVID-19, caused by SARS-CoV-2 infection, warrants immediate investigation for therapy options. Here the authors show, using epithelial and air-liquid interface cultures, that SARS-CoV-2 hijacks host cell metabolism to facilitate viral replication, and that inhibition of mTORC1, a master metabolic regulator, suppresses viral replication.
- Peter J. Mullen
- , Gustavo Garcia Jr
- & Heather R. Christofk
-
Article
| Open Access
Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway
ASXL1 mutations are frequently found in age-related clonal haemaotopoiesis (CH), but how they drive CH is unclear. Here the authors show that expression of C-terminal truncated ASXL1 in haematopoietic stem cells (HSCs) leads to Akt de-ubiquitination, activated Akt/mTOR signaling, and aberrant HSC proliferation.
- Takeshi Fujino
- , Susumu Goyama
- & Toshio Kitamura
-
Article
| Open Access
Stable inheritance of Sinorhizobium meliloti cell growth polarity requires an FtsN-like protein and an amidase
In Sinorhizobium bacteria, cell elongation takes place only at new cell poles, generated by cell division. Here, Krol et al. show that an FtsN-like protein and a peptidoglycan amidase are crucial for reliable selection of the new cell pole as cell elongation zone.
- Elizaveta Krol
- , Lisa Stuckenschneider
- & Anke Becker
-
Article
| Open Access
Emr1 regulates the number of foci of the endoplasmic reticulum-mitochondria encounter structure complex
Interorganelle membrane contact sites between the endoplasmic reticulum and mitochondria can be mediated with the ER-mitochondria encounter structure (ERMES) complex, though precise regulation is unclear. Here, the authors report that the number of ERMES foci is regulated by the previously uncharacterized mitochondrial membrane protein Emr1.
- Faiz Rasul
- , Fan Zheng
- & Chuanhai Fu
-
Article
| Open Access
A network-based framework for shape analysis enables accurate characterization of leaf epidermal cells
While cell shape is crucial for function and development of organisms, versatile frameworks for cell shape quantification, comparison, and classification remain underdeveloped. Here, the authors use a network-based framework for Arabidopsis leaf epidermal cell shape characterization and classification.
- Jacqueline Nowak
- , Ryan Christopher Eng
- & Zoran Nikoloski
-
Article
| Open Access
Structural insights into TSC complex assembly and GAP activity on Rheb
Tuberous sclerosis complex (TSC) regulates cell growth by controlling the activity of mTORC1. The structure of human TSC complex reveals an arch-shaped, asymmetric architecture and a 2:2:1 stoichiometry of TSC1, TSC2, and TBC1D7 subunits and suggests a mechanism by which TSC2 accelerates GTP hydrolysis against a small GTPase Rheb.
- Huirong Yang
- , Zishuo Yu
- & Yanhui Xu
-
Article
| Open Access
Phase imaging with computational specificity (PICS) for measuring dry mass changes in sub-cellular compartments
Quantitative phase imaging suffers from a lack of specificity in label-free imaging. Here, the authors introduce Phase Imaging with Computational Specificity (PICS), a method that combines phase imaging with machine learning techniques to provide specificity in unlabeled live cells with automatic training.
- Mikhail E. Kandel
- , Yuchen R. He
- & Gabriel Popescu
-
Article
| Open Access
Gap junctions amplify spatial variations in cell volume in proliferating tumor spheroids
Cell proliferation is regulated by cell volume, but it is unclear how individual cancer cells coordinate to regulate cell volumes in 3D clusters. Here the authors propose a mechano-osmotic model to analyse the exchange of fluid and ions between connected cells and their environment in response to proliferation-induced solid stress.
- Eoin McEvoy
- , Yu Long Han
- & Vivek B. Shenoy
-
Article
| Open Access
A protein tertiary structure mimetic modulator of the Hippo signalling pathway
Targeting the interaction between transcription factor TEAD and its co-repressor VGL4 is an attractive strategy to chemically modulate Hippo signaling. Here, the authors develop a proteomimetic with stabilized tertiary structure that inhibits the TEAD:VGL4 interaction in vitro and in cells.
- Hélène Adihou
- , Ranganath Gopalakrishnan
- & Herbert Waldmann
-
Article
| Open Access
Autophagy facilitates adaptation of budding yeast to respiratory growth by recycling serine for one-carbon metabolism
Autophagy is important during stress and development, but how the metabolites generated are used by the cell remains unclear. Here, the authors demonstrate that budding yeast require autophagy to provide serine for one-carbon metabolism during the switch from glycolytic to respiratory growth.
- Alexander I. May
- , Mark Prescott
- & Yoshinori Ohsumi
-
Article
| Open Access
mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability
mTORC1 is a key mediator of drug resistance and also regulates autophagy. In this study, the authors demonstrate that cancer cells with acquired drug resistance exibit metabolic vulnerabilities mediated by high levels of mTORC1 and the consequent inhibition of autophagy.
- Niklas Gremke
- , Pierfrancesco Polo
- & Thorsten Stiewe
-
Article
| Open Access
Defining the ATPome reveals cross-optimization of metabolic pathways
Energy metabolism and ATP levels are controlled by an interlocking network of pathways. Here, the authors apply a genome-wide CRISPR screen to define genes that increase or decrease ATP levels to define the “ATPome”, a map of pathways that contribute to cellular ATP regulation.
- Neal K. Bennett
- , Mai K. Nguyen
- & Ken Nakamura
An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway