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https://www.readbyqxmd.com/read/28344588/atlsg1-2-regulates-leaf-growth-by-affecting-cell-proliferation-and-the-onset-of-endoreduplication-and-synergistically-interacts-with-atnmd3-during-cell-proliferation-process
#1
Huayan Zhao, Shiyou Lü, Liming Xiong
AtLSG1-2 is a circularly permuted GTPase required for ribosome biogenesis and recently shown to be involved in early leaf development, although it was unclear how AtLSG1-2 affects leaf growth. Here, we found that atlsg1-2 mutants had reduced leaf size as a result of decreased cell size and cell number. Leaf kinematic analysis and CYCB1;1::GUS expression pattern in atlsg1-2 mutant indicated that loss of function of AtLSG1-2 delays the transition from cell division to cell expansion. Decreases in ploidy levels and trichome branch number suggest that AtLSG1-2 deficiency suppresses endoreduplication...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28344327/mevalonate-cascade-inhibition-by-simvastatin-induces-the-intrinsic-apoptosis-pathway-via-depletion-of-isoprenoids-in-tumor-cells
#2
Javad Alizadeh, Amir A Zeki, Nima Mirzaei, Sandipan Tewary, Adel Rezaei Moghadam, Aleksandra Glogowska, Pandian Nagakannan, Eftekhar Eftekharpour, Emilia Wiechec, Joseph W Gordon, Fred Y Xu, Jared T Field, Ken Y Yoneda, Nicholas J Kenyon, Mohammad Hashemi, Grant M Hatch, Sabine Hombach-Klonisch, Thomas Klonisch, Saeid Ghavami
The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28342870/the-rab-gtpase-rab18-modulates-macroautophagy-and-proteostasis
#3
Anne Feldmann, Fazilet Bekbulat, Heike Huesmann, Sarah Ulbrich, Jörg Tatzelt, Christian Behl, Andreas Kern
Macroautophagy is a conserved degradative pathway and its deterioration is linked to disturbances in cellular proteostasis and multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy in primary human fibroblasts. The knockdown of RAB18 results in a decreased autophagic activity, while its overexpression enhances the degradative pathway. Importantly, this function of RAB18 is dependent on RAB3GAP1 and RAB3GAP2, which might act as RAB GEFs and stimulate the activity of the RAB GTPase. Moreover, the knockdown of RAB18 deteriorates proteostasis and results in the intracellular accumulation of ubiquitinated degradation-prone proteins...
March 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28342293/ribosomal-protein-l7-l12-is-required-for-gtpase-translation-factors-ef-g-rf3-and-if2-to-bind-in-their-gtp-state-to-70s-ribosomes
#4
Markus A Carlson, Bassam G Haddad, Amanda J Weis, Colby S Blackwood, Catherine D Shelton, Michelle E Wuerth, Justin D Walter, P Clint Spiegel
Ribosomal protein L7/L12 is associated with translation initiation, elongation and termination by the 70S ribosome. The GTPase activity of EF-G requires the presence of L7/L12, which is critical for ribosomal translocation. Here, we have developed new methods for the complete depletion of L7/L12 from E. coli 70S ribosomes to analyze the effect of L7/L12 on the activities of the GTPase factors EF-G, RF3, IF2 and LepA. Upon removal of L7/L12 from ribosomes, the GTPase activities of EF-G, RF3 and IF2 decreased to basal levels while the activity of LepA decreased marginally...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28341635/sept7b-is-required-for-the-subcellular-organization-of-cardiomyocytes-and-cardiac-function-in-zebrafish
#5
Surjya Narayan Dash, Suneeta Narumanchi, Jere Paavola, Sanni Perttunen, Hong Wang, Päivi Lakkisto, Ilkka Tikkanen, Sanna Lehtonen
Myofibrils made up of actin and myosin and associated proteins generate the contractile force in muscle and consequently, mutations in these proteins may lead to heart failure. Septins are a conserved family of small GTPases that associate with actin filaments, microtubules and cellular membranes. Despite the importance of septins in cytoskeleton organization, their role in cardiomyocyte organization and function is poorly characterized. Here we show that septin 7 is expressed in both embryonic and adult zebrafish heart, and elucidate the physiological significance of sept7b, the zebrafish ortholog of human septin 7, in the heart in embryonic and larval zebrafish...
March 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28339090/inhibition-of-farnesyl-pyrophosphate-synthase-attenuates-high-glucose%C3%A2-induced-vascular-smooth-muscle-cells-proliferation
#6
Guo-Ping Chen, Xiao-Qin Zhang, Tao Wu, Jie Han, Dan Ye
The proliferation of vascular smooth muscle cells (VSMCs) is one of the main features of atherosclerosis accelerated by hyperglycemia. Our previous studies found that farnesyl pyrophosphate synthase (FPPS, EC 2.5.1.10), an essential enzyme in the mevalonate pathway, was upregulated in aorta media from diabetic mice along with the process of atherosclerosis. However, the exact role of FPPS in high glucose‑induced proliferation of VSMCs is largely unclear. In our study, we found that alendronate (an FPPS inhibitor) attenuated diabetic accelerated atherosclerosis in vivo and suppressed high glucose‑induced VSMCs proliferation in vitro...
March 23, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28337369/role-of-notch-signaling-pathway-in-pancreatic-cancer
#7
REVIEW
Jiankun Gao, Bo Long, Zhiwei Wang
Pancreatic cancer (PC) is one of the highly aggressive malignancies in the United States. It has been shown that multiple signaling pathways are involved in the pathogenesis of PC, such as JNK, PI3K/AKT, Rho GTPase, Hedgehog (Hh) and Skp2. In recent years, accumulated evidence has demonstrated that Notch signaling pathway plays critical roles in the development and progression of PC. Therefore, in this review we discuss the recent literature regarding the function and regulation of Notch in the pathogenesis of PC...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28336235/tyrosine-phosphorylation-of-rab7-by-src-kinase
#8
Xiaosi Lin, Jiaming Zhang, Lingqiu Chen, Yongjun Chen, Xiaohui Xu, Wanjin Hong, Tuanlao Wang
The small molecular weight GTPase Rab7 is a key regulator for late endosomal/lysosomal membrane trafficking, it was known that Rab7 is phosphorylated, but the corresponding kinase and the functional regulation of Rab7 phosphorylation remain unclear. We provide evidence here that Rab7 is a substrate of Src kinase, and is tyrosine-phosphorylated by Src, withY183 residue of Rab7 being the optimal phosphorylation site for Src. Further investigations demonstrated that the tyrosine phosphorylation of Rab7 depends on the guanine nucleotide binding activity of Rab7 and the activity of Src kinase...
March 20, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28336130/organizers-and-activators-cytosolic-nox-proteins-impacting-on-vascular-function
#9
REVIEW
Katrin Schröder, Norbert Weissmann, Ralf P Brandes
NADPH oxidases of the Nox family are important enzymatic sources of reactive oxygen species (ROS) in the cardiovascular system. Of the 7 members of the Nox family, at least three depend for their activation on specific cytosolic proteins. These are p47phox and its homologue NoxO1 and p67phox and its homologue NoxA1. Also the Rho-GTPase Rac is important but as this protein has many additional functions, it will not be covered here. The Nox1 enzyme is preferentially activated by the combination of NoxO1 with NoxA1, whereas Nox2 gains highest activity with p47phox together with p67phox...
March 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28336063/probing-cdc42-polarization-dynamics-in-budding-yeast-using-a-biosensor
#10
Satoshi Okada, Mid Eum Lee, Erfei Bi, Hay-Oak Park
Cdc42 is a small guanosine triphosphatase (GTPase) that plays a central role in polarity development in diverse cell types. Since the activity of Cdc42 is dynamically controlled in time and space, it is required to develop a biosensor to monitor its activation in vivo. In this chapter, we describe the construction and usage of a simple and robust biosensor for monitoring active Cdc42 in budding yeast. This affinity-based biosensor uses a red fluorescent protein fused to a Cdc42- and Rac-interactive binding motif from one of the Cdc42 effector proteins...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28334931/rgf1p-rho1p-gef-is-required-for-double-strand-break-repair-in-fission-yeast
#11
Elvira Manjón, Tomás Edreira, Sofía Muñoz, Yolanda Sánchez
Rho GTPases are conserved molecules that control cytoskeletal dynamics. These functions are expedited by Rho GEFs that stimulate the release of GDP to enable GTP binding, thereby allowing Rho proteins to initiate intracellular signaling. How Rho GEFs and Rho GTPases protect cells from DNA damage is unknown. Here, we explore the extreme sensitivity of a deletion mutation in the Rho1p exchange factor Rgf1p to the DNA break/inducing antibiotic phleomycin (Phl). The Rgf1p mutant cells are defective in reentry into the cell cycle following the induction of severe DNA damage...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334866/c9orf72-and-rab7l1-regulate-vesicle-trafficking-in-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#12
Yoshitsugu Aoki, Raquel Manzano, Yi Lee, Ruxandra Dafinca, Misako Aoki, Andrew G L Douglas, Miguel A Varela, Chaitra Sathyaprakash, Jakub Scaber, Paola Barbagallo, Pieter Vader, Imre Mäger, Kariem Ezzat, Martin R Turner, Naoki Ito, Samanta Gasco, Norihiko Ohbayashi, Samir El Andaloussi, Shin'ichi Takeda, Mitsunori Fukuda, Kevin Talbot, Matthew J A Wood
A non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS/FTD pathogenesis remains unclear. Here, we report a novel disease mechanism arising due to the interaction of C9ORF72 with the RAB7L1 GTPase to regulate vesicle trafficking. Endogenous interaction between C9ORF72 and RAB7L1 was confirmed in human SH-SY5Y neuroblastoma cells...
February 23, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334226/loss-of-cannabinoid-cb-1-receptors-induces-cortical-migration-malformations-and-increases-seizure-susceptibility
#13
Javier Díaz-Alonso, Adán de Salas-Quiroga, Juan Paraíso-Luna, Daniel García-Rincón, Patricia P Garcez, Maddy Parsons, Clara Andradas, Cristina Sánchez, François Guillemot, Manuel Guzmán, Ismael Galve-Roperh
Neuronal migration is a fundamental process of brain development, and its disruption underlies devastating neurodevelopmental disorders. The transcriptional programs governing this process are relatively well characterized. However, how environmental cues instruct neuronal migration remains poorly understood. Here, we demonstrate that the cannabinoid CB 1 receptor is strictly required for appropriate pyramidal neuron migration in the developing cortex. Acute silencing of the CB 1 receptor alters neuronal morphology and impairs radial migration...
October 5, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/28331068/mutations-in-efl1-an-sbds-partner-are-associated-with-infantile-pancytopenia-exocrine-pancreatic-insufficiency-and-skeletal-anomalies-in-a-shwachman-diamond-like-syndrome
#14
Polina Stepensky, Montserrat Chacón-Flores, Katherine H Kim, Omar Abuzaitoun, Arnulfo Bautista-Santos, Natalia Simanovsky, Dritan Siliqi, Davide Altamura, Alfonso Méndez-Godoy, Abril Gijsbers, Adeeb Naser Eddin, Talia Dor, Joel Charrow, Nuria Sánchez-Puig, Orly Elpeleg
BACKGROUND: For the final step of the maturation of the ribosome, the nascent 40S and 60S subunits are exported from the nucleus to the cell cytoplasm. To prevent premature association of these ribosomal subunits, eukaryotic initiation factor 6 (eIF6) binds the 60S subunit within the nucleus. Its release in the cytoplasm requires the interaction of EFL1 and SDBS proteins. In Shwachman-Diamond syndrome (SDS), a defective SDBS protein prevents eIF6 eviction, inhibiting its recycle to the nucleus and subsequent formation of the active 80S ribosome...
March 22, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28330155/purification-and-characterization-of-rga2-a-rho2-gtpase-activating-protein-from-tinospora-cordifolia
#15
Mohd Amir, Mohammad Aasif Dar, Wahiduzzaman, Asimul Islam, Faizan Ahmad, Md Imtaiyaz Hassan
Rho GTPases activating protein 2 (RGA2) is primarily involved in the modulation of numerous morphological events in eukaryotes. It protects plants by triggering the defense system which restricts the pathogen growth. This is the first report on the isolation, purification and characterization of RGA2 from the stems of Tinospora cordifolia, a medicinal plant. The RGA2 was purified using simple two-step process using DEAE-Hi-Trap FF and Superdex 200 chromatography columns, with a high yield. The purity of RGA2 was confirmed by SDS-PAGE and identified by MALDI-TOF/MS...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28328290/cross-talk-between-rho-gtpases-and-pi3k-in-the-neutrophil
#16
Barry McCormick, Julia Y Chu, Sonja Vermeren
Neutrophils are short-lived, abundant peripheral blood leukocytes that provide a first line of defense against bacterial and fungal infections whilst also being a key part of the inflammatory response. Chemokines induce neutrophil recruitment to inflammatory sites, where neutrophils perform a number of diverse functions that are aimed at fighting infections. Neutrophil effector functions are tightly regulated processes that are governed by an array of intracellular signaling pathways and initiated by receptor-ligand binding events...
March 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28326929/dendritic-spine-dysgenesis-in-superficial-dorsal-horn-sensory-neurons-after-spinal-cord-injury
#17
Xiaoyu C Cao, Laura W Pappalardo, Stephen G Waxman, Andrew M Tan
Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our previous work has demonstrated a structure-function link between dendritic spine dysgenesis on nociceptive sensory neurons in the intermediate zone, laminae IV/V, and chronic pain in central nervous system and peripheral nervous system injury models of neuropathic pain. To extend these findings, we performed a follow-up structural analysis to assess whether dendritic spine remodeling occurs on superficial dorsal horn neurons located in lamina II after spinal cord injury...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326341/cdc42-is-crucial-for-facial-and-palatal-formation-during-craniofacial-development
#18
Mutsuko Oshima-Nakayama, Atsushi Yamada, Tamaki Kurosawa, Ryo Aizawa, Dai Suzuki, Yoshiro Saito, Hidetoshi Kassai, Yuki Sato, Matsuo Yamamoto, Tatsuo Shirota, Atsu Aiba, Koutaro Maki, Ryutaro Kamijo
Craniofacial deformities with multifactorial etiologies, such as cleft palate and facial dysmorphism, represent some of the most frequent congenital birth defects seen in humans. Their pathogeneses are often related to cranial neural crest (CNC) cells. During CNC cell migration, changes in cell shape and formation, as well as maintenance of subcellular structures, such as filopodia and lamellipodia, are dependent on the complex functions of Rho family small GTPases, which are regulators of actin cytoskeletal organization...
December 2016: Bone Reports
https://www.readbyqxmd.com/read/28325809/the-rab7-effector-plekhm1-binds-arl8b-to-promote-cargo-traffic-to-lysosomes
#19
Rituraj Marwaha, Subhash B Arya, Divya Jagga, Harmeet Kaur, Amit Tuli, Mahak Sharma
Endocytic, autophagic, and phagocytic vesicles move on microtubule tracks to fuse with lysosomes. Small GTPases, such as Rab7 and Arl8b, recruit their downstream effectors to mediate this transport and fusion. However, the potential cross talk between these two GTPases is unclear. Here, we show that the Rab7 effector PLEKHM1 simultaneously binds Rab7 and Arl8b, bringing about clustering and fusion of late endosomes and lysosomes. We show that the N-terminal RUN domain of PLEKHM1 is necessary and sufficient for interaction with Arl8b and its subsequent localization to lysosomes...
March 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28324667/gtpase-activating-protein-elmod2-is-essential-for-meiotic-progression-in-mouse-oocytes
#20
Chun-Xiang Zhou, Li-Ya Shi, Rui-Chao Li, Ya-Hong Liu, Bo-Qun Xu, Jin-Wei Liu, Bo Yuan, Zhi-Xia Yang, Xiao-Yan Ying, Dong Zhang
Meiotic failure in oocytes is the major determinant of human zygote-originated reproductive diseases, the successful accomplishment of meiosis largely relay on the normal functions of many female fertility factors. Elmod2 is a member of the Elmod family with the strongest GAP (GTPase-activating protein) activity; although it was identified as a possible maternal protein, its actual physiologic role in mammalian oocytes has not been elucidated. Herein we reported that among Elmod family proteins, Elmod2 is the most abundant in mouse oocytes, and that inhibition of Elmod2 by specific siRNA caused severe meiotic delay and abnormal chromosomal segregation during anaphase...
March 21, 2017: Cell Cycle
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