Article
Plant Sciences
Khem Raj Ghusinga, Timothy C. Elston, Alan M. Jones
Summary: G-proteins are molecular switches that transmit extracellular signals to intracellular targets. In plants, the role of nucleotide exchange in this process is less critical, but under dynamic conditions, the loss of RGS results in a strong phenotype.
Article
Plant Sciences
Swarup Roy Choudhury, Sona Pandey
Summary: This study reveals a direct regulation of G alpha protein by symbiosis receptor kinase (SymRK) through phosphorylation, which not only affects its activity but also influences the availability of its signaling partners, thereby exerting a two-pronged check on signaling.
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)
Review
Pharmacology & Pharmacy
Xin Xu, Guangyu Wu
Summary: G protein G beta gamma subunits play crucial roles in G protein-coupled receptor signaling and have been targeted for disease treatments. Recent studies have discovered non-canonical activation of G beta gamma at intracellular organelles, particularly the Golgi apparatus, where it regulates cell processes and can be targeted for therapeutic interventions. Inhibiting Golgi-compartmentalized G beta gamma signaling has shown promise in attenuating cardiomyocyte hypertrophy and prostate tumorigenesis.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Plant Sciences
Genki Chaya, Shuhei Segami, Moeka Fujita, Yoichi Morinaka, Yukimoto Iwasaki, Kotaro Miura
Summary: This study reveals that both DEP1 and OsGGC2 genes are positive regulators of plant height and their functions are redundant.
Review
Biochemistry & Molecular Biology
Jan H. Voss, Christa E. Muller
Summary: G protein-coupled receptors are the most important class of drug targets in the human body, transmitting extracellular signals into the cytosol through interaction with Gα proteins. Direct inhibition of Ga protein subunits has been proposed as a novel strategy for treating complex diseases.
CURRENT MEDICINAL CHEMISTRY
(2022)
Review
Plant Sciences
Yijie Wang, Jose Ramon Botella
Summary: As sessile organisms, plants have evolved mechanisms to adapt to environmental fluctuations. Heterotrimeric G proteins play essential roles in the response to stress in plants, regulating multiple signaling pathways. Understanding the functions of G proteins in stress reactions can contribute to the development of resilient crops and global food security.
Article
Microbiology
Miaomiao Ma, Wei Wang, Yue Fei, Hang-Yuan Cheng, Beibei Song, Zhaoyang Zhou, Yan Zhao, Xiaojuan Zhang, Lin Li, She Chen, Jizong Wang, Xiangxiu Liang, Jian-Min Zhou
Summary: Plants use cell surface receptors to recognize immune patterns and activate defenses, but how these receptors regulate immune signaling in the nucleus is not well understood. In this study, the researchers discovered that the kinase BIK1 phosphorylates XLG2, promoting its nuclear translocation and positively regulating antibacterial immunity. XLG2 interacts with nuclear-localized MLKs to control transcriptome programming. MLKs negatively regulate plant immunity in a kinase activity-dependent manner, while XLG2 inhibits MLK kinase activity to promote defense gene expression and antibacterial immunity. These findings reveal a previously unknown pathway and mechanisms by which cell surface receptors regulate transcriptome during pathogen invasion.
CELL HOST & MICROBE
(2022)
Article
Biochemistry & Molecular Biology
Lian Wu, Xiaodong Wang, Zhiwen Yu, Xin Cui, Quan Xu
Summary: This paper reveals the antagonistic regulation of grain yield and quality by two type C G protein gamma subunits, DEP1 and GS3, in rice. Editing the DEP1 gene increases grain number per panicle but has negative effects on taste value, texture properties, and chalkiness-related traits. Editing the GS3 gene decreases grain number per panicle but increases grain length and improves taste value, appearance, texture properties, and Rapid Visco Analyser (RVA) profiles. Molecular design breeding combining gs3 and dep1 alleles further increases grain yield, enhances texture properties and RVA profiles, and improves taste quality.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Yoichiro Kamimura, Masahiro Ueda
Summary: Chemotaxis is the process of cells undergoing directional movement along ambient chemical gradients, playing important roles in human physiology and pathology. Studies on Dictyostelium cells have elucidated the crucial roles of various mechanisms of GPCR signaling in broad range sensing of chemical gradients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
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.
Article
Genetics & Heredity
Santosh Kumar, Andrew C. Olson, Michael R. Koelle
Summary: The study demonstrates the successful insertion of green fluorescent protein (GFP) into G alpha(o) protein in neurons, allowing for in vivo functional studies and facilitating cell biological and biochemical research on G alpha(o). The transgenic expression of G alpha(o)-GFP rescues defects caused by loss of endogenous G alpha(o), such as in egg laying and locomotion behaviors, and also restores body morphology defects. The G alpha(o)-GFP protein can be localized to the plasma membrane of neurons, similar to endogenous G alpha(o), and can be immunoprecipitated for purification of G alpha(o) protein complexes.
G3-GENES GENOMES GENETICS
(2021)
Article
Plant Sciences
Natsumi Maruta, Yuri Trusov, Daisuke Urano, David Chakravorty, Sarah M. Assmann, Alan M. Jones, Jose R. Botella
Summary: XLG2, an unconventional G alpha subunit, plays a major role in plant defense through GTP-independent mechanisms. The XLG2(T476N) variant without GTP binding ability retains interactions with key proteins involved in defense responses, highlighting the diverse functions of XLG2 in Arabidopsis.
Article
Developmental Biology
Farah Saad, David R. Hipfner
Summary: The Hedgehog (Hh) pathway is regulated by G protein-coupled receptors (GPCRs) in Drosophila, with Mthl5 identified as a modulator of this pathway. This suggests potential crosstalk between GPCRs and the Hh pathway in mammals as well.
Article
Biochemistry & Molecular Biology
Clinita E. Randolph, Morgan B. Dwyer, Jenna L. Aumiller, Alethia J. Dixon, Asuka Inoue, Patrick Osei-Owusu, Philip B. Wedegaertner
Summary: Heterotrimeric G proteins are proteins that link activated G protein coupled receptors (GPCRs) to intracellular signaling pathways. YM-254890 (YM) inhibits both GPCR-activated WT alpha q and GPCR-independent alpha qQ209L signaling. YM promotes a redistribution of alpha qQ209L from the plasma membrane to the cytoplasm. Changes in membrane binding impact the ability of YM to inhibit alpha qQ209L, and YM contributes to inhibition of alpha qQ209L by promoting its relocalization.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
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
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
Multidisciplinary Sciences
Malika Faouzi, Ram P. Neupane, Jian Yang, Philip Williams, Reinhold Penner
SCIENTIFIC REPORTS
(2018)
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
Pharmacology & Pharmacy
Lawrence Fourgeaud, Curt Dvorak, Malika Faouzi, John Starkus, Sunil Sandeo, Qi Wang, Brian Lord, Heather Coate, Natalie Taylor, Yingbo He, Ning Qin, Alan Wickenden, Nicholas Carruthers, Timothy W. Lovenberg, Reinhold Penner, Anindya Bhattacharya
EUROPEAN JOURNAL OF PHARMACOLOGY
(2019)
Article
Cell Biology
Osama M. Elzamzamy, Brandon E. Johnson, Wei-Chih Chen, Gangqing Hu, Reinhold Penner, Lori A. Hazlehurst
Summary: The study investigated the treatment mechanism of MTI-101 for multiple myeloma (MM) and found that MTI-101 can induce Ca2+ and Na+ flux through TRPC1 heteromers. The formation of TRPC1-calcium-regulating protein STIM1 complex plays a key role in MTI-101-induced cell death.
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)
