Article
Multidisciplinary Sciences
Kirill D. Nadezhdin, Leonor Correia, Chamali Narangoda, Dhilon S. Patel, Arthur Neuberger, Thomas Gudermann, Maria G. Kurnikova, Vladimir Chubanov, Alexander I. Sobolevsky
Summary: The transient receptor potential channel TRPM7 is a crucial regulator of divalent cation balance in the body, impacting various biological processes such as embryonic development, immune responses, and cell functionalities. It is linked to neuronal and cardiovascular disorders as well as tumor progression, highlighting its potential as a drug target. Using cryo-EM, functional analysis, and molecular dynamics simulations, researchers have unraveled two distinct structural mechanisms behind TRPM7 activation through gain-of-function mutations and the agonist naltriben. These mechanisms exhibit different conformational dynamics and involve different domains. Additionally, the study identifies a binding site for potent and selective inhibitors that stabilize the closed state of TRPM7, paving the way for the development of drugs targeting TRPM7-related channelopathies.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Aline Schuetz, Christin Richter, Petra Weissgerber, Volodymyr Tsvilovskyy, Michael Hesse, Roger Ottenheijm, Frank Zimmermann, Stefanie Buchholz, Rebekka Medert, Sascha Dlugosz, Vladimir Kuryshev, Vladimir Benes, Veit Flockerzi, Bernd K. Fleischmann, Adolfo Cavalie, Marc Freichel
Summary: Early embryogenesis relies on proper regulation of intracellular ion homeostasis, including Ca2+ and Mg2+. Deletion of the TRPM7 channel conducting Ca2+ and Mg2+ is lethal in mouse embryos, with Trpm7(-/-) embryos failing to expand trophoblast cells and not being identifiable in utero at E6.5 or later. The critical role of TRPM7 in trophectoderm cells and their failure during implantation may explain the developmental arrest of Trpm7-deficient mouse embryos.
Review
Cardiac & Cardiovascular Systems
Qing Liu, Suyao Li, Yuran Qiu, Jiayu Zhang, Francisco J. Rios, Zhiguo Zou, Rhian M. Touyz
Summary: Receptor tyrosine kinases are membrane spanning receptors that play important roles in cancer development. Targeted therapies against these receptors have been widely used in cancer treatment, but they can also cause cardiovascular toxicity. This review discusses the implications of tyrosine kinase inhibitors in cardiovascular toxicities and explores the potential role of TRPM7/Mg2+ in mediating these effects.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Biology
Francisco J. Rios, Zhi-Guo Zou, Adam P. Harvey, Katie Y. Harvey, Livia L. Camargo, Karla B. Neves, Sarah E. F. Nichol, Rheure Alves-Lopes, Alexius Cheah, Maram Zahraa, Alexey G. Ryazanov, Lillia Ryazanova, Thomas Gudermann, Vladimir Chubanov, Augusto C. Montezano, Rhian M. Touyz
Summary: TRPM7 deficiency may be an important mechanism underlying cardiovascular and renal diseases caused by hyperaldosteronism, and it is associated with hypomagnesemia.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Jincheng Wang, Weike Li, Zimeng Li, Zhenyu Xue, Yuefang Zhang, Yiting Yuan, Yuhan Shi, Shifang Shan, Wenjian Han, Fei Li, Zilong Qiu
Summary: Strong evidence from human genetic studies links the TAOK1 gene to autism spectrum disorder (ASD). In a Chinese ASD cohort, a de novo frameshifting mutation in the TAOK1 gene was identified. Haploinsufficiency of Taok1 induced autistic-like behaviors in mice and was found to be significantly enriched in the dorsal raphe nucleus (DRN). Genetic deletion of Taok1 in VGlut3-positive neurons of the DRN resulted in mice exhibiting autistic-like behaviors. Reintroducing wild-type Taok1, but not its kinase-dead variant, effectively mitigated the autistic-like behaviors associated with Taok1 haploinsufficiency in adult mice. This work provides critical insights into the etiology of ASD by highlighting the role of Taok1 in regulating social interaction behaviors through its influence in the DRN.
Article
Multidisciplinary Sciences
Inga Andriule, Dalia Pangonyte, Mante Almanaityte, Vaiva Patamsyte, Milda Kupryte, Dainius Karciauskas, Kanigula Mubagwa, Regina Macianskiene
Summary: The study demonstrates the presence and co-expression of TRPM6 and TRPM7 in cardiomyocytes from all chamber walls of the human heart, with increased expression in tissues from patients with ischemic heart disease. This suggests that these channels-enzymes may play a role in the pathophysiology of the disease.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Benjamin P. Luscher, Andreina Schoeberlein, Daniel Surbek, Marc U. Baumann
Summary: In this study, the effect of hyperuricemia during pregnancy on maternal blood pressure and neonatal outcome was investigated using two different murine knockout models. The findings showed that hyperuricemia plays a major role in the pathogenesis of hypertensive pregnancy disorders such as pre-eclampsia, and it also leads to fetal renal tissue injuries and impaired neonatal growth.
Article
Biochemistry & Molecular Biology
Zhiyong Bai, Jianlin Feng, Gijs A. C. Franken, Namariq Al'Saadi, Na Cai, Albert S. Yu, Liping Lou, Yuko Komiya, Joost G. J. Hoenderop, Jeroen H. F. de Baaij, Lixia Yue, Loren W. Runnels
Summary: Members of the CNNM family selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. They also possess separate TRPM7-independent Mg2+ efflux activities that contribute to the control of cellular Mg2+ homeostasis. This study provides new insights into the mechanisms by which CNNMs regulate cellular magnesium levels.
Article
Biochemistry & Molecular Biology
Sara Rosendahl, Rima Sulniute, Julia Persson, Sebastian Forsberg, Rebecka Haggvik, Viktor Drewsen, Cecilia Koskinen Holm, Elin Kindstedt, Pernilla Lundberg
Summary: Juvenile and adult male mice lacking CCR3 receptors exhibit a thin cortical bone phenotype, which is not observed in female mice. This suggests a sex hormone-related role of CCR3 in cortical bone turnover.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Laura Wilson, Alice E. Pollard, Lucy Penfold, Phillip J. Muckett, Chad Whilding, Mohammad Bohlooly-Y, Patricia Wilson, David Carling
Summary: AMP-activated protein kinase (AMPK) has emerged as an attractive therapeutic target for metabolic diseases. This study found that chronic AMPK activation leads to a polycystic kidney phenotype, showing dysregulated AMPK signaling is a contributing factor in cystogenesis.
Article
Cell Biology
Astrid M. Schoppa, Xiangxu Chen, Jan-Moritz Ramge, Anna Vikman, Verena Fischer, Melanie Haffner-Luntzer, Jana Riegger, Jan Tuckermann, Karin Scharffetter-Kochanek, Anita Ignatius
Summary: Osteoporosis is a common disease associated with oxidative stress, and the decrease of SOD2 may lead to bone loss and osteoporosis.
DISEASE MODELS & MECHANISMS
(2022)
Article
Endocrinology & Metabolism
Pearl A. Sutter, Sangita Karki, Ilan Crawley, Vijender Singh, Kathrin M. Bernt, David W. Rowe, Stephen J. Crocker, Dashzeveg Bayarsaihand, Rosa M. Guzzo
Summary: Chromatin modifying enzymes like Dot1L play vital roles in skeletal development and maintenance by regulating growth plate chondrocyte proliferation, extracellular matrix production, and bone formation. Loss of Dot1L expression results in limb abnormalities and impaired trabecular bone formation in young mice, highlighting the crucial regulatory control it provides for endochondral bone morphology and growth.
Article
Multidisciplinary Sciences
Shoupeng Wei, Sarah Hertle, Rainer Spanagel, Ainhoa Bilbao
Summary: The study reveals that female mice are more vulnerable to the addictive properties of sugar than male mice, showing higher binge and long-term, excessive drinking, a more pronounced relapse-like drinking following deprivation, as well as higher persistence and motivation for sugar. No sex differences were seen in a compulsivity test or reward sensitivity following extended sugar consumption.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Andrii Kovalenko, Andres Sanin, Kosmas Kosmas, Long Zhang, Ji Wang, Elie W. Akl, Krinio Giannikou, Clemens Kemena Probst, Thomas Robert Hougard, Ryan W. Rue, Vera P. Krymskaya, John M. Asara, Hilaire C. Lam, David J. Kwiatkowski, Elizabeth P. Henske, Harilaos Filippakis
Summary: The study identifies DGKA as supporting macropinocytosis in TSC2-deficient cells to maintain phospholipid homeostasis and promote proliferation, suggesting ritanserin as a new therapeutic approach for TSC and lymphangioleiomyomatosis.
Article
Biology
Flavia S. Mueller, Rene Amport, Tina Notter, Sina M. Schalbetter, Han-Yu Lin, Zuzana Garajova, Parisa Amini, Ulrike Weber-Stadlbauer, Enni Markkanen
Summary: This study found a link between deficient DNA repair leading to unrepaired DNA damage in the forebrain and the development of neuropsychiatric disorders. The effects of this DNA damage on anxiety-like behaviors were found to be sex-dependent, and alterations to the GABAergic neurotransmitter system may contribute to this effect.
Article
Neurosciences
Susanna Zierler, Adriana Sumoza-Toledo, Sayuri Suzuki, Fionan O. Duill, Lillia V. Ryazanova, Reinhold Penner, Alexey G. Ryazanov, Andrea Fleig
JOURNAL OF PHYSIOLOGY-LONDON
(2016)
Article
Physiology
Gerhard Sponder, Lucia Mastrototaro, Katharina Kurth, Lucia Merolle, Zheng Zhang, Nasrin Abdulhanan, Alina Smorodchenko, Katharina Wolf, Andrea Fleig, Reinhold Penner, Stefano Iotti, Joerg R. Aschenbach, Juergen Vormann, Martin Kolisek
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2016)
Article
Multidisciplinary Sciences
Chad Jansen, Jaya Sahni, Sayuri Suzuki, F. David Horgen, Reinhold Penner, Andrea Fleig
SCIENTIFIC REPORTS
(2016)
Article
Plant Sciences
John G. Starkus, Peter Poerzgen, Kristine Layugan, Kelly Galbraith Kawabata, Jun-Ichi Goto, Sayuri Suzuki, George Myers, Michelle Kelly, Reinhold Penner, Andrea Fleig, F. David Horgen
JOURNAL OF NATURAL PRODUCTS
(2017)
Editorial Material
Neurosciences
Andrea Fleig, Anant B. Parekh
JOURNAL OF PHYSIOLOGY-LONDON
(2017)
Article
Neurosciences
Malika Faouzi, Tatiana Kilch, F. David Horgen, Andrea Fleig, Reinhold Penner
JOURNAL OF PHYSIOLOGY-LONDON
(2017)
Article
Biology
Xavier Sisquella, Thomas Nebr, Jennifer K. Thompson, Lachlan Whitehead, Brian M. Malpede, Nichole D. Salinas, Kelly Rogers, Niraj H. Tolia, Andrea Fleig, Joseph O'Neill, Wai-Hong Timm, F. David Horgen, Alan F. Cowman
Article
Biochemistry & Molecular Biology
Sayuri Suzuki, Annette Lis, Carsten Schmitz, Reinhold Penner, Andrea Fleig
CELLULAR AND MOLECULAR LIFE SCIENCES
(2018)
Article
Cell Biology
Andreas Beck, Andrea Fleig, Reinhold Penner, Christine Peinelt
Article
Biochemistry & Molecular Biology
Zheng Zhang, Haijie Yu, Junhao Huang, Malika Faouzi, Carsten Schmitz, Reinhold Penner, Andrea Fleig
JOURNAL OF BIOLOGICAL CHEMISTRY
(2014)
Article
Biochemistry & Molecular Biology
Yan Huang, Tian-Dong Leng, Koichi Inoue, Tao Yang, Mingli Liu, F. David Horgen, Andrea Fleig, Jun Li, Zhi-Gang Xiong
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Neurosciences
Ekaterina Turlova, Christine Y. J. Bae, Marielle Deurloo, Wenliang Chen, Andrew Barszczyk, F. David Horgen, Andrea Fleig, Zhong-Ping Feng, Hong-Shuo Sun
MOLECULAR NEUROBIOLOGY
(2016)
Article
Oncology
Zheng Zhang, Malika Faouzi, Junhao Huang, Dirk Geerts, Haijie Yu, Andrea Fleig, Reinhold Penner
Article
Cell Biology
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, F. Kelly Galbraith Kawabata, David Horgen, Toshihiko Kawamori, Reinhold Penner, Andrea Fleig
CELL COMMUNICATION AND SIGNALING
(2017)