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JOURNAL ARTICLE
Vincenzo Salpietro, Reza Maroofian, Maha S Zaki, Jamie Wangen, Andrea Ciolfi, Sabina Barresi, Stephanie Efthymiou, Angelique Lamaze, Gabriel N Aughey, Fuad Al Mutairi, Aboulfazl Rad, Clarissa Rocca, Elisa Calì, Andrea Accogli, Federico Zara, Pasquale Striano, Majid Mojarrad, Huma Tariq, Edoardo Giacopuzzi, Jenny C Taylor, Gabriela Oprea, Volha Skrahina, Khalil Ur Rehman, Marwa Abd Elmaksoud, Mahmoud Bassiony, Huda G El Said, Mohamed S Abdel-Hamid, Maha Al Shalan, Gohun Seo, Sohyun Kim, Hane Lee, Rin Khang, Mahmoud Y Issa, Hasnaa M Elbendary, Karima Rafat, Nikolaos M Marinakis, Joanne Traeger-Synodinos, Athina Ververi, Mara Sourmpi, Atieh Eslahi, Farhad Khadivi Zand, Mehran Beiraghi Toosi, Meisam Babaei, Adam Jackson, Aida Bertoli-Avella, Alistair T Pagnamenta, Marcello Niceta, Roberta Battini, Antonio Corsello, Chiara Leoni, Francesco Chiarelli, Bruno Dallapiccola, Eissa Ali Faqeih, Krishnaraya K Tallur, Majid Alfadhel, Eman Alobeid, Sateesh Maddirevula, Kshitij Mankad, Siddharth Banka, Ehsan Ghayoor-Karimiani, Marco Tartaglia, Wendy K Chung, Rachel Green, Fowzan S Alkuraya, James E C Jepson, Henry Houlden
The homologous genes GTPBP1 and GTPBP2 encode GTP-binding proteins 1 and 2, which are involved in ribosomal homeostasis. Pathogenic variants in GTPBP2 were recently shown to be an ultra-rare cause of neurodegenerative or neurodevelopmental disorders (NDDs). Until now, no human phenotype has been linked to GTPBP1. Here, we describe individuals carrying bi-allelic GTPBP1 variants that display an identical phenotype with GTPBP2 and characterize the overall spectrum of GTP-binding protein (1/2)-related disorders...
December 19, 2023: American Journal of Human Genetics
#2
JOURNAL ARTICLE
S Udhaya Kumar, C George Priya Doss
The mutant K-Ras with aberrant signaling is the primary cause of several cancers. The proposed study investigated the influence of water molecules in K-Ras crystal structure, where they have a significant function by understanding their residue interaction networks (RINs). We analyzed the RINs of K-Ras with and without water molecules and determined their interaction properties. RINs were developed with the help of StructureViz2 and RINspector; further, the changes in K-Ras backbone flexibility were predicted with the DynaMine...
August 2021: Computers in Biology and Medicine
#3
JOURNAL ARTICLE
Martin J Baker, Ignacio Rubio
Ras and its related small GTPases are important signalling nodes that regulate a wide variety of cellular functions. The active form of these proteins exists in a transient GTP bound state that mediates downstream signalling events. The dysregulation of these GTPases has been associated with the progression of multiple diseases, most prominently cancer and developmental syndromes known as Rasopathies. Determining the activation state of Ras and its relatives has hence been of paramount importance for the investigation of the biochemical functions of small GTPases in the cellular signal transduction network...
2021: Methods in Molecular Biology
#4
JOURNAL ARTICLE
Masanori Ishizaka, Tomohito Gohda, Miyuki Takagi, Keisuke Omote, Yuji Sonoda, Juan Alejandro Oliva Trejo, Rin Asao, Teruo Hidaka, Katsuhiko Asanuma, Satoshi Horikoshi, Yasuhiko Tomino
Rac1, a GTPase of the Rho subfamily, has a crucial role in cytoskeletal architecture, as well as the regulation of cell migration and growth. However, renal injury in mice with podocyte-specific deletion of Rac1 has yet to be elucidated fully due to conflicting findings. Herein, we identified a possible role for Rac1 in podocytes of streptozotocin- (STZ) induced diabetic mice. The urinary albumin/creatinine ratio (ACR) in the knockout (KO) group was significantly higher than that in the wild type (WT) group at any week of age...
November 20, 2015: Biochemical and Biophysical Research Communications
#5
JOURNAL ARTICLE
Motomichi Doi, Hideki Minematsu, Yukihiko Kubota, Kiyoji Nishiwaki, Masaaki Miyamoto
Cell migration and axon guidance require proper regulation of the actin cytoskeleton in response to extracellular guidance cues. Rho/Rac small GTPases are essential regulators of actin remodeling. Caenorhabditis elegans CED-10 is a Rac1 homolog that is required for various cellular morphological changes and migration events and is under the control of several guidance signaling pathways. There is still considerable uncertainty regarding events following the activation of guidance receptors by extracellular signals and the regulation of actin dynamics based on spatiotemporally restricted Rac activity...
August 2013: Development
#6
JOURNAL ARTICLE
Rin Asaoka, Tomohiro Uemura, Sho Nishida, Toru Fujiwara, Takashi Ueda, Akihiko Nakano
RAB11 GTPases, widely conserved members of RAB small GTPases, have evolved in a unique way in plants; plant RAB11 has notable diversity compared with animals and yeast. Recently, we have shown that members of RABA1, a subgroup in Arabidopsis RAB11 group, are required for salinity stress tolerance. To obtain a clue to understand its underlying mechanism, here we investigate whether RABA1 regulates sodium transport across the plasma membrane and accumulation in the vacuole. The results indicate that the raba1 quadruple mutant is not defective in the import and intracellular distribution of sodium, implying that RABA1 members are involved in a more indirect way in the responses to salinity stress...
September 2013: Plant Signaling & Behavior
#7
REVIEW
Geng-Xian Shi, Weikang Cai, Douglas A Andres
Ras family small GTPases serve as binary molecular switches to regulate a broad array of cellular signaling cascades, playing essential roles in a vast range of normal physiological processes, with dysregulation of numerous Ras-superfamily G-protein-dependent regulatory cascades underlying the development of human disease. However, the physiological function for many "orphan" Ras-related GTPases remain poorly characterized, including members of the Rit subfamily GTPases. Rit is the founding member of a novel branch of the Ras subfamily, sharing close homology with the neuronally expressed Rin and Drosophila Ric GTPases...
October 2013: Cellular Signalling
#8
JOURNAL ARTICLE
Weikang Cai, Jennifer L Rudolph, Tomoko Sengoku, Douglas A Andres
Rit, along with Rin and Drosophila Ric, comprises the Rit subfamily of Ras-related small GTPases. Although the cellular functions of many Ras family GTPases are well established, the physiological significance of Rit remains poorly understood. Loss of Rit sensitizes multiple mammalian cell lines and mouse embryonic fibroblasts (MEFs) derived from Rit(-/-) mice to oxidative stress-mediated apoptosis. However, whether Rit-mediated pro-survival signaling extends to other cell types, particularly neurons, is presently unknown...
December 7, 2012: Neuroscience Letters
#9
JOURNAL ARTICLE
Rin Asaoka, Tomohiro Uemura, Jun Ito, Masaru Fujimoto, Emi Ito, Takashi Ueda, Akihiko Nakano
RAB GTPases are key regulators of membrane traffic. Among them, RAB11, a widely conserved sub-group, has evolved in a unique way in plants; plant RAB11 members show notable diversity, whereas yeast and animals have only a few RAB11 members. Fifty-seven RAB GTPases are encoded in the Arabidopsis thaliana genome, 26 of which are classified in the RAB11 group (further divided into RABA1-RABA6 sub-groups). Although several plant RAB11 members have been shown to play pivotal roles in plant-unique developmental processes, including cytokinesis and tip growth, molecular and physiological functions of the majority of RAB11 members remain unknown...
January 2013: Plant Journal
#10
COMMENT
Mar Fernandez-Borja
Endothelial cell adhesion to the extracellular matrix regulates migration and outgrowth of blood vessels during angiogenesis. Cell adhesion is mediated by integrins, which transduce signals from the extracellular environment into the cell and, in turn, are regulated by intracellular signaling molecules. In a paper recently published in Cell Research, Sandri et al. show that RIN2 connects three GTPases, R-Ras, Rab5 and Rac1, to promote endothelial cell adhesion through the regulation of integrin internalization and Rac1 activation...
October 2012: Cell Research
#11
JOURNAL ARTICLE
Elena Feraru, Mugurel I Feraru, Rin Asaoka, Tomasz Paciorek, Riet De Rycke, Hirokazu Tanaka, Akihiko Nakano, Jirí Friml
Constitutive endocytic recycling is a crucial mechanism allowing regulation of the activity of proteins at the plasma membrane and for rapid changes in their localization, as demonstrated in plants for PIN-FORMED (PIN) proteins, the auxin transporters. To identify novel molecular components of endocytic recycling, mainly exocytosis, we designed a PIN1-green fluorescent protein fluorescence imaging-based forward genetic screen for Arabidopsis thaliana mutants that showed increased intracellular accumulation of cargos in response to the trafficking inhibitor brefeldin A (BFA)...
July 2012: Plant Cell
#12
COMPARATIVE STUDY
Deanna M Navaroli, Zachary H Stevens, Zeljko Uzelac, Luke Gabriel, Michael J King, Lawrence M Lifshitz, Harald H Sitte, Haley E Melikian
Dopaminergic signaling and plasticity are essential to numerous CNS functions and pathologies, including movement, cognition, and addiction. The amphetamine- and cocaine-sensitive dopamine (DA) transporter (DAT) tightly controls extracellular DA concentrations and half-life. DAT function and surface expression are not static but are dynamically modulated by membrane trafficking. We recently demonstrated that the DAT C terminus encodes a PKC-sensitive internalization signal that also suppresses basal DAT endocytosis...
September 28, 2011: Journal of Neuroscience
#13
JOURNAL ARTICLE
Weikang Cai, Jennifer L Rudolph, Susan M W Harrison, Ling Jin, Aubrey L Frantz, Douglas A Harrison, Douglas A Andres
Ras-related small GTP-binding proteins control a wide range of cellular processes by regulating a variety of effector pathways, including prominent roles in the control of mitogen-activated protein kinase (MAPK) cascades. Although the regulatory role(s) for many Ras family GTPases are well established, the physiological function for the Rit/Rin subfamily has been lacking. Here, using both knockout mice and Drosophila models, we demonstrate an evolutionarily conserved role for Rit subfamily GTPases (mammalian Rit and Rin, and the Drosophila RIC homologue) in governing survival in response to oxidative stress...
September 2011: Molecular Biology of the Cell
#14
JOURNAL ARTICLE
Hiroaki Kajiho, Kyoko Sakurai, Tomohiro Minoda, Manabu Yoshikawa, Satoshi Nakagawa, Shinichi Fukushima, Kenji Kontani, Toshiaki Katada
The small GTPase Rab5, which cycles between GDP-bound inactive and GTP-bound active forms, plays essential roles in membrane budding and trafficking in the early endocytic pathway. Rab5 is activated by various vacuolar protein sorting 9 (VPS9) domain-containing guanine nucleotide exchange factors. Rab21, Rab22, and Rab31 (members of the Rab5 subfamily) are also involved in the trafficking of early endosomes. Mechanisms controlling the activation Rab5 subfamily members remain unclear. RIN (Ras and Rab interactor) represents a family of multifunctional proteins that have a VPS9 domain in addition to Src homology 2 (SH2) and Ras association domains...
July 8, 2011: Journal of Biological Chemistry
#15
JOURNAL ARTICLE
Geng-Xian Shi, Ling Jin, Douglas A Andres
Pituitary adenylate cyclase-activating polypeptide 38 (PACAP38) is a potent neuropeptide that acts through G-protein-coupled receptors. While it is well established that PACAP mediates both neurotrophic and neurodevelopmental effects, the signaling cascades that underlie these diverse actions remain incompletely characterized. Here we show that the Ras-related Rin GTP-binding protein, a GTPase that is expressed predominantly in neurons, is regulated by PACAP38 signaling, and loss-of-function analysis demonstrates that Rin makes an essential contribution to PACAP38-mediated pheochromocytoma cell differentiation...
August 2008: Molecular and Cellular Biology
#16
JOURNAL ARTICLE
Manabu Yoshikawa, Hiroaki Kajiho, Kyoko Sakurai, Tomohiro Minoda, Satoshi Nakagawa, Kenji Kontani, Toshiaki Katada
The small GTPase Rab5 plays a key role in early endocytic pathway, and its activation requires guanine-nucleotide exchange factors (GEFs). Rab5-GEFs share a conserved VPS9 domain for the GEF action, and RIN3 containing additional domains, such as Src-homology 2, RIN-family homology (RH), and Ras-association (RA), was identified as a new Rab5-GEF. However, precise functions of the additional domains and the activation mechanism of RIN3 remain unknown. Here, we found tyrosine-phosphorylation signals are involved in the Rab5-GEF activation...
July 18, 2008: Biochemical and Biophysical Research Communications
#17
JOURNAL ARTICLE
Kota Saito, Hiroaki Kajiho, Yasuhiro Araki, Hiroshi Kurosu, Kenji Kontani, Hiroshi Nishina, Toshiaki Katada
The small GTPase Rab5 plays important roles in membrane budding and trafficking in the early endocytic pathways, and the activation of this GTPase is mediated by several guanine nucleotide exchange factors (GEFs) at each of the transport steps. The RIN family has been identified as GEFs for Rab5 and shown to possess unique biochemical properties. The RIN family preferentially interacts with an activated form of Rab5, although it enhances guanine nucleotide exchange reaction. Moreover, biochemical analysis indicates that the RIN family functions as a tetramer...
2005: Methods in Enzymology
#18
JOURNAL ARTICLE
Geng-Xian Shi, Jiahuai Han, Douglas A Andres
In neuronal precursor cells, the magnitude and longevity of mitogen-activated protein (MAP) kinase cascade activation contribute to the nature of the cellular response, differentiation, or proliferation. However, the mechanisms by which neurotrophins promote prolonged MAP kinase signaling are not well understood. Here we defined the Rin GTPase as a novel component of the regulatory machinery contributing to the selective integration of MAP kinase signaling and neuronal development. Rin is expressed exclusively in neurons and is activated by neurotrophin signaling, and loss-of-function analysis demonstrates that Rin makes an essential contribution to nerve growth factor (NGF)-mediated neuronal differentiation...
November 11, 2005: Journal of Biological Chemistry
#19
COMPARATIVE STUDY
Christine Hartwig, Andres Veske, Sarka Krejcova, Georg Rosenberger, Ulrich Finckh
BACKGROUND: Plexins, known to date as receptors of semaphorins, are implicated in semaphorin-mediated axon repulsion and growth cone collapse. However, subtype-specific functions of the majority of the nine members of the mammalian plexin family are largely unknown. In order to investigate functional properties of B-plexins, we analyzed the expression of human and murine plexin B3 and expressed full-length human plexins B2 (B2) and B3 (B3) in NIH-3T3 cells. RESULTS: Unexpectedly, B3 strongly and B2 moderately stimulate neurite outgrowth of primary murine cerebellar neurons...
August 25, 2005: BMC Neuroscience
#20
JOURNAL ARTICLE
Mitsunobu Hoshino, Tamotsu Yoshimori, Shun Nakamura
The novel small GTPases Rin and Rit are close relatives of Ras, and recent studies show that they play a role in mediating neuronal differentiation. However, the direct effectors of Rin and Rit have yet to be fully characterized. Here we showed that Rin and Rit directly bind to the PDZ domain of PAR6, a cell polarity-regulating protein, in a GTP-dependent manner both in vivo and in vitro. Moreover, Rin and Rit can form a ternary complex consisting of PAR6 and Rac/Cdc42, members of the Rho family of small GTPases modulating cell growth and polarity...
June 17, 2005: Journal of Biological Chemistry
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