4.5 Article

PI3K-p110-alpha-subtype signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2

期刊

JOURNAL OF NEUROCHEMISTRY
卷 130, 期 2, 页码 255-267

出版社

WILEY
DOI: 10.1111/jnc.12718

关键词

brain; cerebral cortex; insulin; neuron; PI3K-isoform; PI3K-subunit

资金

  1. EC [LSHG-CT-2007-036894]
  2. Schlieben-Lange-Programm
  3. BMBF GerontoSys II - NephAge [031 5896A]
  4. University of Groningen, NL
  5. Stiftung der Deutschen Wirtschaft
  6. German Research Foundation DFG
  7. Excellence Initiative of the German Research Foundation [EXC 294]
  8. Excellence Initiative of the German Research Foundation (Spemann Graduate School) [GSC-4]
  9. Freiburg institute for Advanced Studies FRIAS Junior Fellowship

向作者/读者索取更多资源

Development of the cerebral cortex is controlled by growth factors among which transforming growth factor beta (TGF beta) and insulin-like growth factor 1 (IGF1) have a central role. The TGF beta- and IGF1-pathways cross-talk and share signalling molecules, but in the central nervous system putative points of intersection remain unknown. We studied the biological effects and down-stream molecules of TGF beta and IGF1 in cells derived from the mouse cerebral cortex at two developmental time points, E13.5 and E16.5. IGF1 induces PI3K, AKT and the mammalian target of rapamycin complexes (mTORC1/mTORC2) primarily in E13.5-derived cells, resulting in proliferation, survival and neuronal differentiation, but has small impact on E16.5-derived cells. TGF beta has little effect at E13.5. It does not activate the PI3K- and mTOR-signalling network directly, but requires its activity to mediate neuronal differentiation specifically at E16.5. Our data indicate a central role of mTORC2 in survival, proliferation as well as neuronal differentiation of E16.5-derived cortical cells. mTORC2 promotes these cellular processes and is under control of PI3K-p110-alpha signalling. PI3K-p110-beta signalling activates mTORC2 in E16.5-derived cells but it does not influence cell survival, proliferation and differentiation. This finding indicates that different mTORC2 subtypes may be implicated in cortical development and that these subtypes are under control of different PI3K isoforms

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

Article Biochemical Research Methods

PEtab-Interoperable specification of parameter estimation problems in systems biology

Leonard Schmiester, Yannik Schaelte, Frank T. Bergmann, Tacio Camba, Erika Dudkin, Janine Egert, Fabian Froehlich, Lara Fuhrmann, Adrian L. Hauber, Svenja Kemmer, Polina Lakrisenko, Carolin Loos, Simon Merkt, Wolfgang Mueller, Dilan Pathirana, Elba Raimundez, Lukas Refisch, Marcus Rosenblatt, Paul L. Stapor, Philipp Staedter, Dantong Wang, Franz-Georg Wieland, Julio R. Banga, Jens Timmer, Alejandro F. Villaverde, Sven Sahle, Clemens Kreutz, Jan Hasenauer, Daniel Weindl

Summary: Reproducibility and reusability of results in data-based modeling studies are essential, and PEtab provides a standardized format for specification of parameter estimation problems in systems biology. The format has been implemented by eight software tools with hundreds of users, showing great potential impact in the modeling and algorithm development community.

PLOS COMPUTATIONAL BIOLOGY (2021)

Review Cell Biology

Review article for CTR special issue edited by C. Schachtrup Title of Special Issue: Modulating scar formation for improving brain repair Loss-of-function manipulations to identify roles of diverse glia and stromal cells during CNS scar formation

Shalaka Wahane, Michael V. Sofroniew

Summary: Scar formation in the CNS involves complex interactions among multiple types of CNS glia and non-neural stromal cells, and dysfunctions of these cells may contribute to different neuropathological mechanisms. Insights into specific neuropathological mechanisms and potential interventions are emerging as potential targets for diverse CNS disorders.

CELL AND TISSUE RESEARCH (2022)

Article Infectious Diseases

Preventing COVID-19 outbreaks through surveillance testing in healthcare facilities: a modelling study

Tim Litwin, Jens Timmer, Mathias Berger, Andreas Wahl-Kordon, Matthias J. Mueller, Clemens Kreutz

Summary: This study establishes an individual-based model to compare different testing strategies and finds that active testing in mental health hospitals and similar facilities can significantly reduce the number of COVID-19 outbreaks.

BMC INFECTIOUS DISEASES (2022)

Article Multidisciplinary Sciences

Divergent transcriptional regulation of astrocyte reactivity across disorders

Joshua E. Burda, Timothy M. O'Shea, Yan Ao, Keshav B. Suresh, Shinong Wang, Alexander M. Bernstein, Ashu Chandra, Sandeep Deverasetty, Riki Kawaguchi, Jae H. Kim, Sarah McCallum, Alexandra Rogers, Shalaka Wahane, Michael Sofroniew

Summary: This study reveals the regulatory mechanism of genes associated with astrocyte reactivity through biological and informatic analyses. These genes show heterogeneity across different central nervous system disorders and are regulated by transcriptional regulators. By modulating reactivity, these transcriptional regulators can alter the outcome of the disorders and may serve as therapeutic targets.

NATURE (2022)

Article Multidisciplinary Sciences

PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling

Maria Thuermer, Andre Gollowitzer, Helmut Pein, Konstantin Neukirch, Elif Gelmez, Lorenz Waltl, Natalie Wielsch, Rene Winkler, Konstantin Loeser, Julia Grander, Madlen Hotze, Sonke Harder, Annika Doeding, Martina Messner, Fabiana Troisi, Maximilian Ardelt, Hartmut Schlueter, Johanna Pachmayr, Oscar Gutierrez-Gutierrez, Karl Lenhard Rudolph, Kathrin Thedieck, Ulrike Schulze-Spaete, Cristina Gonzalez-Estevez, Christian Kosan, Ales Svatos, Marcel Kwiatkowski, Andreas Koeberle

Summary: The study reveals that PI(18:1/18:1) is a signaling lipid derived from SCD1 that connects fatty acid unsaturation with stress responses, regulating stress adaption, protecting against cell death, and promoting proliferation.

NATURE COMMUNICATIONS (2022)

Article Chemistry, Analytical

Comparative Assessment of Quantification Methods for Tumor Tissue Phosphoproteomics

Yang Zhang, Benjamin Dreyer, Natalia Govorukhina, Alexander M. Heberle, Sasa Koncarevic, Christoph Krisp, Christiane A. . Opitz, Pauline Pfander, Rainer Bischoff, Hartmut Schlueter, Marcel Kwiatkowski, Kathrin Thedieck, Peter L. Horvatovich

Summary: The study compares three different quantitation techniques for tumor tissue phosphoproteomics and highlights the strengths and limitations of each method. The choice of quantitative methodology is critical for study design and comparison of published cancer phosphoproteomes. The results provide a resource for the design and analysis of quantitative phosphoproteomic studies in cancer research and diagnostics.

ANALYTICAL CHEMISTRY (2022)

Article Cardiac & Cardiovascular Systems

Fine-Tuning Cardiac Insulin-Like Growth Factor 1 Receptor Signaling to Promote Health and Longevity

Mahmoud Abdellatif, Viktoria Trummer-Herbst, Alexander Martin Heberle, Alina Humnig, Tobias Pendl, Sylvere Durand, Giulia Cerrato, Sebastian J. Hofer, Moydul Islam, Julia Voglhuber, Jose Miguel Ramos Pittol, Oliver Kepp, Gerald Hoefler, Albrecht Schmidt, Peter P. Rainer, Daniel Scherr, Dirk von Lewinski, Egbert Bisping, Julie R. McMullen, Abhinav Diwan, Tobias Eisenberg, Frank Madeo, Kathrin Thedieck, Guido Kroemer, Simon Sedej

Summary: This study suggests a biphasic relationship between insulin-like growth factor 1 receptor (IGF1R) signaling and cardiac health. Higher IGF1R signaling in young mice leads to declining cardiac function and shorter lifespan, while lower IGF1R signaling improves cardiac function and extends lifespan in aging mice.

CIRCULATION (2022)

Editorial Material Immunology

cDC1 to cDC2: Everything I do, Ido1 it for you

Mirja Tamara Prentzell, Christiane A. Opitz

Summary: The IDO1-Kyn-AHR axis has been identified as a metabolic signaling pathway through which conventional dendritic cell subsets communicate and induce tolerogenicity.

IMMUNITY (2022)

Article Multidisciplinary Sciences

Circulating multimeric immune complexes contribute to immunopathology in COVID-19

Jakob Ankerhold, Sebastian Giese, Philipp Kolb, Andrea Maul-Pavicic, Reinhard E. Voll, Nathalie Goppert, Kevin Ciminski, Clemens Kreutz, Achim Lother, Ulrich Salzer, Wolfgang Bildl, Tim Welsink, Nils G. Morgenthaler, Andrea Busse Grawitz, Florian Emmerich, Daniel Steinmann, Daniela Huzly, Martin Schwemmle, Hartmut Hengel, Valeria Falcone

Summary: Severe or critical COVID-19 patients exhibit dysregulated immune response with high levels of SARS-CoV-2 specific IgG antibodies. Excessive activation of FcγRIIIA/CD16A is observed in these patients, and two independent ligands are identified as the mediators of extreme activation. Soluble circulating IgG immune complexes (sICs), similar to those found in systemic lupus erythematosus, are detected in about 80% of severe and critical COVID-19 patients.

NATURE COMMUNICATIONS (2022)

Article Biochemical Research Methods

Proteome Coverage after Simultaneous Proteo-Metabolome Liquid-Liquid Extraction

Alienke van Pijkeren, Anna-Sophia Egger, Madlen Hotze, Elisabeth Zimmermann, Tobias Kipura, Julia Grander, Andre Gollowitzer, Andreas Koeberle, Rainer Bischoff, Kathrin Thedieck, Marcel Kwiatkowski

Summary: Proteomics and metabolomics play vital roles in systems biology, and the simultaneous extraction of proteome and metabolome from the same sample is important. This study compared the performance of different surfactants and urea for proteome extraction and found that urea showed the best efficiency for simultaneous proteo-metabolome analysis.

JOURNAL OF PROTEOME RESEARCH (2023)

Article Biochemical Research Methods

Phosphoproteomics Profiling Defines a Target Landscape of the Basophilic Protein Kinases AKT, S6K, and RSK in Skeletal Myotubes

Anna L. Fricke, Wignand W. D. Muhlhauser, Lena Reimann, Johannes P. Zimmermann, Christa Reichenbach, Bettina Knapp, Christian D. Peikert, Alexander M. Heberle, Erik Faessler, Sascha Schauble, Udo Hahn, Kathrin Thedieck, Gerald Radziwill, Bettina Warscheid

Summary: Phosphorylation-dependent signal transduction involving protein kinases AKT, S6K, and RSK plays a crucial role in regulating skeletal muscle cells. However, the specific targets of these kinases are still not completely understood. In this study, we used quantitative phosphoproteomics to investigate the effects of kinase inhibition in skeletal myotubes, revealing AKT-RAF cross talk, a negative feedback loop of RSK on ERK, and a potential connection between RSK and PI3K signaling. Our findings provide valuable insights into the kinase target landscape and the intricate signaling network involved in skeletal muscle regulation, including muscle development, integrity, and translation processes.

JOURNAL OF PROTEOME RESEARCH (2023)

Article Medicine, General & Internal

Rebalancing of mitochondrial homeostasis through an NAD+- SIRT1 pathway preserves intestinal barrier function in severe malnutrition

Catriona Ling, Christian J. Versloot, Matilda E. Arvidsson Kvissberg, Guanlan Hu, Nathan Swain, Jose M. Horcas-Nieto, Emily Miraglia, Mehakpreet K. Thind, Amber Farooqui, Albert Gerding, Karen van Eunen, Mirjam H. Koster, Niels J. Kloosterhuis, Lijun Chi, YueYing ChenMi, Miriam Langelaar-Makkinje, Celine Bourdon, Jonathan Swann, Marieke Smit, Alain de Bruin, Sameh A. Youssef, Marjon Feenstra, Theo H. van Dijk, Kathrin Thedieck, Johan W. Jonker, Peter K. Kim, Barbara M. Bakker, Robert H. J. Bandsma

Summary: Severe malnutrition leads to structural and functional changes in the intestine, increasing the risk of infection and mortality. This study reveals the mechanisms underlying malnutrition enteropathy, including dysregulation of autophagy and mitochondrial homeostasis, as well as abnormalities in reactive oxygen species. The findings suggest that nicotinamide supplementation and modulation of SIRT1 and mTORC1 pathways may ameliorate malnutrition enteropathy in children with severe malnutrition.

EBIOMEDICINE (2023)

Review Microbiology

Gut Microbiota in Diagnosis, Therapy and Prognosis of Cholangiocarcinoma and Gallbladder Carcinoma-A Scoping Review

Ann-Kathrin Lederer, Hannah Rasel, Eva Kohnert, Clemens Kreutz, Roman Huber, Mohamed Tarek Badr, Patricia K. E. Dellweg, Fabian Bartsch, Hauke Lang

Summary: This article provides a scoping review of the current research on the associations between gut microbiota and diagnosis, progression, and prognosis of biliary tract cancer. The findings suggest differences in gut microbiota between biliary tract cancer patients and healthy controls, but no specific species have been identified. However, due to methodological flaws in most of the studies, there is currently insufficient evidence to support the use of gut microbiota diagnostics in the management of biliary tract cancer.

MICROORGANISMS (2023)

Article Cell Biology

Cardiac PI3K p110α attenuation delays aging and extends lifespan

Mahmoud Abdellatif, Tobias Eisenberg, Alexander Martin Heberle, Kathrin Thedieck, Guido Kroemer, Simon Sedej

Summary: Phosphoinositide 3-kinase (PI3K) is a key molecule that controls cellular metabolism and growth. In model organisms, reducing PI3K signaling can extend lifespan, but this effect is sex-specific and may increase the risk of cardiac disease in young mice. However, experimental attenuation of PI3K signaling in aged mice can slow down cardiac function decline and extend lifespan. In humans, increased PI3K signaling has been observed in failing hearts.

CELL STRESS (2022)

Article Biochemistry & Molecular Biology

Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study

Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu

Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.

JOURNAL OF NEUROCHEMISTRY (2024)