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Table of Contents

November 2022 | Volume 5, No. 11

Reviews

  • Building in vitro models of the brain to understand the role of <em>APOE</em> in Alzheimer’s disease
    Open Access
    Building in vitro models of the brain to understand the role of APOE in Alzheimer’s disease

    Rebecca L Pinals, Li-Huei Tsai

    Rebecca L Pinals ... Li-Huei Tsai

    Published 27 September 2022

    Human induced pluripotent stem cell (hiPSC)–based models of the brain will be key to unraveling the role of APOE ɛ4 in the interconnected cellular changes underlying Alzheimer’s disease.

Research Articles

  • Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension
    Open Access
    Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension

    Jonathan Florentin, Jingsi Zhao, Yi-Yin Tai, Wei Sun, Lee L Ohayon, Scott P O’Neil, Anagha Arunkumar, Xinyi Zhang, Jianhui Zhu, Yassmin Al Aaraj, Annie Watson, John Sembrat, Mauricio Rojas, Stephen Y Chan, Partha Dutta

    Jonathan Florentin ... Partha Dutta

    Published 22 June 2022

    The key pathogenic features of pulmonary hypertension are endothelial apoptosis and vascular inflammation, which are caused by the down-regulation of Amphiregulin, accompanied by HIF-1a and BAD-mediated up-regulation of the target genes such as RRP1B, PHB2, and NCOA6.

  • Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome
    Open Access
    Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome

    Francisco Bustos, Sunil Mathur, Carmen Espejo-Serrano, Rachel Toth, C James Hastie, Satpal Virdee, Greg M Findlay

    Francisco Bustos ... Greg M Findlay

    Published 28 June 2022

    The authors use photocrosslinking activity-based probes to monitor RNF12/RLIM E3 ubiquitin ligase activity and report the impact of Tonne-Kalscheuer syndrome (TOKAS) patient variants on catalysis.

  • Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants
    Open Access
    Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants

    Laura Strohm, Zehan Hu, Yongwon Suk, Alina Rühmkorf, Erin Sternburg, Vanessa Gattringer, Henrick Riemenschneider, Riccardo Berutti, Elisabeth Graf, Jochen H Weishaupt, Monika S Brill, Angelika B Harbauer, Dorothee Dormann, Jörn Dengjel, Dieter Edbauer, Christian Behrends

    Laura Strohm ... Christian Behrends

    Published 1 July 2022

    Analysis of ALS patient-derived and engineered cells revealed that mutant UBQLN2 increases mRNA and protein of MAP1B which is mediated by dephosphorylation of FUS within its RNA-binding domain.

  • Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models
    Open Access
    Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models

    Merry Chen, Julie Vincent, Alexis Ezeanii, Saurabh Wakade, Shobha Yerigenahally, Danielle E Mor

    Merry Chen ... Danielle E Mor

    Published 5 July 2022

    This study offers new Caenorhabditis elegans models in which feeding with α-synuclein pre-formed fibrils results in prion-like aggregation of host α-synuclein and dopamine neuron degeneration, and these disease phenotypes are regulated by the heparan sulfate proteoglycan pathway.

  • Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
    Open Access
    Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome

    Lilli Winter, Monika Kustermann, Büsra Ernhofer, Harald Höger, Reginald E Bittner, Wolfgang M Schmidt

    Lilli Winter ... Wolfgang M Schmidt

    Published 5 July 2022

    This study demonstrates that the muscular dystrophy-associated proteins dystrophin, utrophin, dysferlin, and calpain-3 localize to the centrosome and that their absence leads to excess centrosomes, compromised nuclear morphology, impaired centrosome orientation, and defective microtubule nucleation.

  • CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7
    Open Access
    CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7

    Yong Zi Tan, Yazan M Abbas, Jing Ze Wu, Di Wu, Kristine A Keon, Geoffrey G Hesketh, Stephanie A Bueler, Anne-Claude Gingras, Carol V Robinson, Sergio Grinstein, John L Rubinstein

    Yong Zi Tan ... John L Rubinstein

    Published 6 July 2022

    The structure of mammalian V-ATPase with mEAK-7 shows how a TLDc domain-containing protein can bind the proton pump to form an activity-sensitive interaction.

  • Identification and characterization of a membrane receptor that binds to human STC1
    Open Access
    Identification and characterization of a membrane receptor that binds to human STC1

    Hin Ting Wan, Alice HM Ng, Wang Ka Lee, Feng Shi, Chris Kong-Chu Wong

    Hin Ting Wan ... Chris Kong-Chu Wong

    Published 7 July 2022

    A study using TriCEPS-based ligand–receptor methodology and surface plasmon resonance assays identified that human stanniocalcin-1 binds to insulin-like growth factor-2 receptors in human leukemia monocytic cells with high affinity.

  • KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cells
    Open Access
    KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cells

    Yu Mashima, Hayato Nohira, Hiroki Sugihara, Brian David Dynlacht, Tetsuo Kobayashi, Hiroshi Itoh

    Yu Mashima ... Hiroshi Itoh

    Published 8 July 2022

    Depletion of the centrosomal kinesin KIF24, known to restrain the assembly of primary cilia, suppresses multipolar spindle formation by clustering centrosomes in centrosome-amplified PDAC cells.

  • STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer
    Open Access
    STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

    Julia E Lefler, Catherine B MarElia-Bennett, Katie A Thies, Blake E Hildreth, Sudarshana M Sharma, Jason R Pitarresi, Lu Han, Caroline Everett, Christopher Koivisto, Maria C Cuitino, Cynthia D Timmers, Elizabeth O’Quinn, Melodie Parrish, Martin J Romeo, Amanda J Linke, G Aaron Hobbs, Gustavo Leone, Denis C Guttridge, Teresa A Zimmers, Gregory B Lesinski, Michael C Ostrowski

    Julia E Lefler ... Michael C Ostrowski

    Published 8 July 2022

    Using a dual recombinase mouse model of pancreatic cancer, investigators uncover genetic evidence for the role of STAT3 signaling in cancer-associated fibroblasts in promoting tumor progression and an immunosuppressive microenvironment.

  • PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance
    Open Access
    PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance

    Kevin Tabury, Mehri Monavarian, Eduardo Listik, Abigail K Shelton, Alex Seok Choi, Roel Quintens, Rebecca C Arend, Nadine Hempel, C Ryan Miller, Balázs Györrfy, Karthikeyan Mythreye

    Kevin Tabury ... Karthikeyan Mythreye

    Published 12 July 2022

    PVT1 is a YAP1 dependent stress responsive lncRNA that promotes ovarian cancer metastasis and chemoresistance, making PVT1 a promising therapeutic target.

  • Lack of bombesin receptor–activated protein attenuates bleomycin-induced pulmonary fibrosis in mice
    Open Access
    Lack of bombesin receptor–activated protein attenuates bleomycin-induced pulmonary fibrosis in mice

    Hui Wang, Wenrui Zhang, Rujiao Liu, Jiaoyun Zheng, Xueping Yao, Hui Chen, Jie Wang, Horst Christian Weber, Xiaoqun Qin, Yang Xiang, Chi Liu, Huijun Liu, Lang Pan, Xiangping Qu

    Hui Wang ... Xiangping Qu

    Published 12 July 2022

    Enhanced autophagic activity in fibroblasts due to lack of BRAP homologous protein might contribute to the resistance to pulmonary fibrosis in mice.

  • The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program
    Open Access
    The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program

    Xiaokang Wang, Wojciech Rosikiewicz, Yurii Sedkov, Baisakhi Mondal, Tanner Martinez, Satish Kallappagoudar, Andrey Tvardovskiy, Richa Bajpai, Beisi Xu, Shondra M Pruett-Miller, Robert Schneider, Hans-Martin Herz

    Xiaokang Wang ... Hans-Martin Herz

    Published 12 July 2022

    The MLL3/4 histone methyltransferase complexes and the histone deacetylase complex MiDAC regulate the histone mark H4K20ac to calibrate gene expression of a common set of target genes.

  • ScRNA-seq expression of <em>IFI27</em> and <em>APOC2</em> identifies four alveolar macrophage superclusters in healthy BALF
    Open Access
    ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF

    Xin Li, Fred W Kolling, Daniel Aridgides, Diane Mellinger, Alix Ashare, Claudia V Jakubzick

    Xin Li ... Claudia V Jakubzick

    Published 12 July 2022

    There are at least 14 AM subtypes; their frequency, along with other immune cells, is highly conserved across individuals, suggesting a specific niche exists for each leukocyte population.

  • ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1
    Open Access
    ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1

    A Jane Bardwell, Beibei Wu, Kavita Y Sarin, Marian L Waterman, Scott X Atwood, Lee Bardwell

    A Jane Bardwell ... Lee Bardwell

    Published 13 July 2022

    As a mechanism of crosstalk, potentially relevant to cancer and developmental signaling, ERK2 MAP kinase phosphorylates the Hedgehog-pathway transcription factor GLI1 on three sites, promoting release of the negative regulator SUFU and the consequent activation of GLI1.

  • Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ<sub>42</sub> toxicity
    Open Access
    Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity

    Victoria L Hewitt, Leonor Miller-Fleming, Madeleine J Twyning, Simonetta Andreazza, Francesca Mattedi, Julien Prudent, Franck Polleux, Alessio Vagnoni, Alexander J Whitworth

    Victoria L Hewitt ... Alexander J Whitworth

    Published 13 July 2022

    The authors provide the first description of the impact of reducing pdzd8-mediated mito–ER contacts which prolongs lifespan, reduces age-related locomotor decline, and protects against mitochondrial toxins. pdzd8 loss is also protective against neuronal toxicity from Aβ42.

  • Comparative functional genomics identifies unique molecular features of EPSCs
    Open Access
    Comparative functional genomics identifies unique molecular features of EPSCs

    Vikas Malik, Ruge Zang, Alejandro Fuentes-Iglesias, Xin Huang, Dan Li, Miguel Fidalgo, Hongwei Zhou, Jianlong Wang

    Vikas Malik ... Jianlong Wang

    Published 12 August 2022

    The authors provide a comprehensive resource on proteomics, transcriptomic, and epigenetic level details of EPSCs to shed light on possible molecular pathways regulating their expanded pluripotency potential.

  • <em>Cdh5</em>-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing
    Open Access
    Cdh5-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing

    Yan Zhang, Henrik Ortsäter, Ines Martinez-Corral, Taija Mäkinen

    Yan Zhang ... Taija Mäkinen

    Published 12 August 2022

    Temporally restricted lineage tracing reveals a non-venous source of dermal lymphatic vessels and highlights Cre induction strategy as a critical parameter for stage-specific cell labeling.

  • Molecular insights into high-altitude adaption and acclimatisation of <em>Aporrectodea caliginosa</em>
    Open Access
    Molecular insights into high-altitude adaption and acclimatisation of Aporrectodea caliginosa

    Iain Perry, Szabolcs Balazs Hernadi, Luis Cunha, Stephen Short, Angela Marchbank, David J Spurgeon, Pablo Orozco-terWengel, Peter Kille

    Iain Perry ... Peter Kille

    Published 17 August 2022

    A megabase genome assembly for Aporrectodea caliginosa is presented with transcriptomic and SNP-based evidence for acclimatisation and adaption to extreme weather conditions found at high altitude.

  • FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration
    Open Access
    FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration

    Zhenyu Zhu, Qingsheng Hou, Bishi Wang, Changhao Li, Luguang Liu, Weipeng Gong, Jie Chai, Hongliang Guo, Yanhan Jia

    Zhenyu Zhu ... Yanhan Jia

    Published 18 August 2022

    FKBP4 controls mitochondrial respiration via modulating COA6-mediated biogenesis and activity of mitochondrial complex IV, thereby regulating 5-fluorouracil sensitivity in colon cancer.

  • <em>Magel2</em> knockdown in hypothalamic POMC neurons innervating the medial amygdala reduces susceptibility to diet-induced obesity
    Open Access
    Magel2 knockdown in hypothalamic POMC neurons innervating the medial amygdala reduces susceptibility to diet-induced obesity

    Yuna Choi, Hyeon-Young Min, Jiyeon Hwang, Young-Hwan Jo

    Yuna Choi ... Young-Hwan Jo

    Published 25 August 2022

    Magel2 knockdown in ARCPOMC neurons innervating the MeA reduces body weight in mice fed with HFD. This effect is associated with increased locomotor activity that is abolished by central GPER blockade.

  • Semaphorin 6D–expressing mesenchymal cells regulate IL-10 production by ILC2s in the lung
    Open Access
    Semaphorin 6D–expressing mesenchymal cells regulate IL-10 production by ILC2s in the lung

    Maiko Naito, Yoshimitsu Nakanishi, Yasutaka Motomura, Hyota Takamatsu, Shohei Koyama, Masayuki Nishide, Yujiro Naito, Mayuko Izumi, Yumiko Mizuno, Yuta Yamaguchi, Satoshi Nojima, Daisuke Okuzaki, Atsushi Kumanogoh

    Maiko Naito ... Atsushi Kumanogoh

    Published 29 August 2022

    Group 2 innate lymphoid cells (ILC2s) have features specific to the niches in which they reside, and we found that semaphorin 6D signaling in the lung niche controls IL-10 production by ILC2s.

  • The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans
    Open Access
    The human RNA polymerase I structure reveals an HMG-like docking domain specific to metazoans

    Julia L Daiß, Michael Pilsl, Kristina Straub, Andrea Bleckmann, Mona Höcherl, Florian B Heiss, Guillermo Abascal-Palacios, Ewan P Ramsay, Katarina Tlučková, Jean-Clement Mars, Torben Fürtges, Astrid Bruckmann, Till Rudack, Carrie Bernecky, Valérie Lamour, Konstantin Panov, Alessandro Vannini, Tom Moss, Christoph Engel

    Julia L Daiß ... Christoph Engel

    Published 1 September 2022

    We characterize the human RNA polymerase I by evolutionary biochemistry and cryo-EM revealing a built-in structural domain that apparently serves as transcription factor–binding platform in metazoans.

  • Dose-dependent phosphorylation and activation of Hh pathway transcription factors
    Open Access
    Dose-dependent phosphorylation and activation of Hh pathway transcription factors

    Mengmeng Zhou, Yuhong Han, Bing Wang, Yong Suk Cho, Jin Jiang

    Mengmeng Zhou ... Jin Jiang

    Published 5 September 2022

    The Hh gradient is translated into a phosphorylation gradient of Ci/Gli at multiple Fu/CK1 phosphorylation sites, which progressively increases CiA/GliA activity by gradually alleviating Sufu-mediated inhibition.

  • Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior
    Open Access
    Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior

    Carla Igual Gil, Bethany M Coull, Wenke Jonas, Rachel N Lippert, Susanne Klaus, Mario Ost

    Carla Igual Gil ... Mario Ost

    Published 6 September 2022

    Muscle mitochondrial stress signals to the brain via hindbrain-specific GFRAL receptor signaling to promote hypothalamic CRH induction, which associates with GFRAL-dependent modulation of systemic energy metabolism, diurnal food intake, and anxiety-like behavior.

  • Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models
    Open Access
    Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models

    Kristel Kemper, Ellis Gielen, Peter Boross, Mischa Houtkamp, Theo S Plantinga, Stefanie AH de Poot, Saskia M Burm, Maarten L Janmaat, Louise A Koopman, Edward N van den Brink, Rik Rademaker, Dennis Verzijl, Patrick J Engelberts, David Satijn, A Kate Sasser, Esther CW Breij

    Kristel Kemper ... Esther CW Breij

    Published 8 September 2022

    This study provides in-depth insight into the mechanism of action and in vivo pharmacodynamic markers of a CD3x5T4 bispecific antibody in preclinical in vitro and in vivo solid cancer models.

  • α-Actinin-4 recruits Shp2 into focal adhesions to potentiate ROCK2 activation in podocytes
    Open Access
    α-Actinin-4 recruits Shp2 into focal adhesions to potentiate ROCK2 activation in podocytes

    Chien-Chun Tseng, Ru-Hsuan Zheng, Ting-Wei Lin, Chih-Chiang Chou, Yu-Chia Shih, Shao-Wei Liang, Hsiao-Hui Lee

    Chien-Chun Tseng ... Hsiao-Hui Lee

    Published 12 September 2022

    α-Actinin-4 is crucial in the regulation of Shp2 FA targeting to enhance ROCK2-mediated actomyosin contractility and thereby strengthening cell adhesion and cytoskeletal architecture in podocytes.

  • Sibling rivalry among the ZBTB transcription factor family: homodimers versus heterodimers
    Open Access
    Sibling rivalry among the ZBTB transcription factor family: homodimers versus heterodimers

    Sofia Piepoli, Sarah Barakat, Liyne Nogay, Büşra Şimşek, Umit Akkose, Hakan Taskiran, Nazife Tolay, Melike Gezen, Canberk Yarkın Yeşilada, Mustafa Tuncay, Ogün Adebali, Canan Atilgan, Batu Erman

    Sofia Piepoli ... Batu Erman

    Published 12 September 2022

    BTB domains potentially can form homo- or heterodimers. The study examines the dimerization choice of several BTB domains and finds only one heterodimer, while all tested pairs can homodimerize.

  • Gain-of-function genetic screens in human cells identify SLC transporters overcoming environmental nutrient restrictions
    Open Access
    Gain-of-function genetic screens in human cells identify SLC transporters overcoming environmental nutrient restrictions

    Manuele Rebsamen, Enrico Girardi, Vitaly Sedlyarov, Stefania Scorzoni, Konstantinos Papakostas, Manuela Vollert, Justyna Konecka, Bettina Guertl, Kristaps Klavins, Tabea Wiedmer, Giulio Superti-Furga

    Manuele Rebsamen ... Giulio Superti-Furga

    Published 16 September 2022

    The authors present a CRISPRa-based gain-of-function approach to systematically uncover solute carriers sustaining cellular fitness upon limiting amino acid concentrations.

  • Translatome profiling in fatal familial insomnia implicates TOR signaling in somatostatin neurons
    Open Access
    Translatome profiling in fatal familial insomnia implicates TOR signaling in somatostatin neurons

    Susanne Bauer, Lars Dittrich, Lech Kaczmarczyk, Melvin Schleif, Rui Benfeitas, Walker S Jackson

    Susanne Bauer ... Walker S Jackson

    Published 3 October 2022

    Bauer and colleagues report that among the six neuron types studied, somatostatin neurons have an unexpectedly strong and similar response to two distinct genetic prion diseases before disease onset.

Corrections

  • Open Access
    Correction: The intracellular pathogen Francisella escapes from adaptive immunity by metabolic adaptation

    Kensuke Shibata, Takashi Shimizu, Mashio Nakahara, Emi Ito, Francois Legoux, Shotaro Fujii, Yuka Yamada, Makoto Furutani-Seiki, Olivier Lantz, Sho Yamasaki, Masahisa Watarai, Mutsunori Shirai

    Kensuke Shibata ... Mutsunori Shirai

    Published 10 October 2022

    This study shows that this metabolic adaptation allows the intracellular bacterial pathogen Francisella tularensis to escape recognition by the host adaptive immunity.

  • Correction: CDKL3 promotes osteosarcoma progression by activating Akt/PKB
    Open Access
    Correction: CDKL3 promotes osteosarcoma progression by activating Akt/PKB

    Aina He, Lanjing Ma, Yujing Huang, Haijiao Zhang, Wei Duan, Zexu Li, Teng Fei, Junqing Yuan, Hao Wu, Liguo Liu, Yueqing Bai, Wentao Dai, Yonggang Wang, Hongtao Li, Yong Sun, Yaling Wang, Chunyan Wang, Ting Yuan, Qingcheng Yang, Songhai Tian, Min Dong, Ren Sheng, Dongxi Xiang

    Aina He ... Dongxi Xiang

    Published 21 October 2022

    This study demonstrates that CDKL3 regulates Akt activation and its downstream targets to promote OS progression, creating a therapeutically targetable vulnerability in treatment of OS.

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Volume 5, No. 11
November 2022
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