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https://www.readbyqxmd.com/read/29098326/sumoylation-controls-stem-cell-proliferation-and-regional-cell-death-through-hedgehog-signaling-in-planarians
#1
Manish Thiruvalluvan, Paul G Barghouth, Assaf Tsur, Limor Broday, Néstor J Oviedo
Mechanisms underlying anteroposterior body axis differences during adult tissue maintenance and regeneration are poorly understood. Here, we identify that post-translational modifications through the SUMO (Small Ubiquitin-like Modifier) machinery are evolutionarily conserved in the Lophotrocozoan Schmidtea mediterranea. Disruption of SUMOylation in adult animals by RNA-interference of the only SUMO E2 conjugating enzyme Ubc9 leads to a systemic increase in DNA damage and a remarkable regional defect characterized by increased cell death and loss of the posterior half of the body...
November 2, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29058184/hyper-sumoylation-of-k-channels-in-sudden-unexplained-death-in-epilepsy-isolation-and-primary-culture-of-dissociated-hippocampal-neurons-from-newborn-mice-for-subcellular-localization
#2
Xu Chen, Shanshan Zhang, Jifang Huang, Wanying Dong, Hui Xiao, Huanjie Shao, Jinke Cheng, Hongmei Wu, Yitao Qi
The physiological characteristics of rat and murine hippocampal neurons are widely studied, especially because of the involvement of the hippocampus in learning, memory, and neurological functions. Primary cultures of hippocampal neurons are commonly used to discover cellular and molecular mechanisms in neurobiology. By isolating and culturing individual hippocampal neurons, neuroscientists are able to investigate the activity of neurons at the individual cell and single synapse level, and to analyze properties related to cellular structure, cellular trafficking, and individual protein subcellular localization or protein-protein interaction using a variety of biochemical techniques...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28713906/chronic-administration-of-sumo%C3%A2-1-has-negative-effects-on-novel-object-recognition-memory-as-well-as-cell-proliferation-and-neuroblast-differentiation-in-the-mouse-dentate-gyrus
#3
Dae Young Yoo, Dae Won Kim, Hyun Jung Kwon, Hyo Young Jung, Sung Min Nam, Jong Whi Kim, Jin Young Chung, Moo-Ho Won, Yeo Sung Yoon, Soo Young Choi, In Koo Hwang
Post‑translational modifications have been associated with developmental and aging processes, as well as in the pathogenesis of certain diseases. The present study aimed to investigate the effects of small ubiquitin‑like modifier 1 (SUMO‑1) on hippocampal dependent memory function, cell proliferation and neuroblast differentiation. To facilitate the delivery of SUMO‑1 into hippocampal neurons, a transactivator of transcription (Tat)‑SUMO‑1 fusion protein was constructed and mice were divided into two groups: A vehicle (Tat peptide)‑treated group and a Tat‑SUMO‑1‑treated group...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713891/hypothermia-exerts-early-neuroprotective-effects-involving-protein-conjugation-of-sumo%C3%A2-2-3-in-a-rat-model-of-middle-cerebral-artery-occlusion
#4
Gang Li, Xiaozhi Liu, Zhiguo Su, Dong Zhang
How hypothermia serves an early protective role against cerebral ischemia remains to be determined. The small ubiquitin‑related modifier protein (SUMO) functions as a post‑translational modification system and SUMO‑2/3 subtypes are often activated in early stress. The present study investigated changes in the protein level of SUMO using western blotting and immunocytochemistry when neurons were exposed to oxygen‑glucose deprivation (OGD) in vitro, as well as in a rat model of middle cerebral artery occlusion (MCAO) in vivo...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28598330/analysis-of-sumo1-conjugation-at-synapses
#5
James A Daniel, Benjamin H Cooper, Jorma J Palvimo, Fu-Ping Zhang, Nils Brose, Marilyn Tirard
SUMO1-conjugation of proteins at neuronal synapses is considered to be a major post-translational regulatory process in nerve cell and synapse function, but the published evidence for SUMO1-conjugation at synapses is contradictory. We employed multiple genetic mouse models for stringently controlled biochemical and immunostaining analyses of synaptic SUMO1-conjugation. By using a knock-in reporter mouse line expressing tagged SUMO1, we could not detect SUMO1-conjugation of seven previously proposed synaptic SUMO1-targets in the brain...
June 9, 2017: ELife
https://www.readbyqxmd.com/read/28501776/inhibition-of-senp3-by-urb597-ameliorates-neurovascular-unit-dysfunction-in-rats-with-chronic-cerebral-hypoperfusion
#6
Da-Peng Wang, Ke-Jia Liu, Graham Kasper, Qi Lin, Jian Hai
Disruption of the neurovascular unit (NVU), induced by chronic cerebral hypoperfusion (CCH), has been broadly found in various neurological disorders. SUMO-specific protease 3 (SENP3) is expressed in neurons, astrocytes, and microglia, and regulates a variety of cell events. However, whether SENP3 is involved in neurovascular injury under the condition of CCH is still elusive. To address this issue, we investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on NVU and the role of SENP3 in this process, as well as the underling mechanisms...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28487986/sumo-1-delays-neuronal-damage-in-the-spinal-cord-following-ischemia-reperfusion
#7
Hyo Young Jung, Dae Won Kim, Hyun Jung Kwon, Dae Young Yoo, In Koo Hwang, Moo-Ho Won, Tack-Geun Cho, Soo Young Choi, Seung Myung Moon
The present study investigated the protective effects of small ubiquitin-like modifier 1 (SUMO-1) on spinal cord ischemic damage in rabbits. A trans‑activator of transcription (Tat)‑SUMO‑1 fusion protein was prepared, and transient spinal cord ischemia was induced by occlusion of the abdominal aorta for 15 min. Vehicle (glycerol) or 1 mg/kg Tat-1-SUMO‑1 was administered intraperitoneally to the rabbits immediately following ischemia/reperfusion. Administration of Tat-SUMO-1 did not lead to significant alterations in arterial blood gases [partial pressure (Pa)CO2 and PaO2], pH, or blood glucose levels prior to ischemia, 10 min after occlusion or 10 min after reperfusion...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28323006/the-role-of-sumoylation-in-cerebral-hypoxia-and-ischemia
#8
REVIEW
Myriam Peters, Betty Wielsch, Johannes Boltze
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism...
July 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28277940/a-single-structurally-conserved-sumoylation-site-in-crmp2-controls-nav1-7-function
#9
Erik Thomas Dustrude, Samantha Perez-Miller, Liberty François-Moutal, Aubin Moutal, May Khanna, Rajesh Khanna
The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant...
July 4, 2017: Channels
https://www.readbyqxmd.com/read/28197918/sumoylation-implications-for-neurodegenerative-diseases
#10
REVIEW
Dina B Anderson, Camila A Zanella, Jeremy M Henley, Helena Cimarosti
The covalent posttranslational modifications of proteins are critical events in signaling cascades that enable cells to efficiently, rapidly and reversibly respond to extracellular stimuli. This is especially important in the CNS where the processes affecting synaptic communication between neurons are highly complex and very tightly regulated. Sumoylation regulates the function and fate of a diverse array of proteins and participates in the complex cell signaling pathways required for cell survival. One of the most complex signaling pathways is synaptic transmission...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28197910/sumo-modification-of-ion-channels
#11
REVIEW
Mark Benson, Jorge A Iñiguez-Lluhí, Jeffrey Martens
Recently, a role for SUMO modification outside of the nucleus has emerged. Although the number of extranuclear proteins known to be sumoylated is comparatively small, ion channels represent one important new class of these proteins. Ion channels are responsible for the control of membrane excitability and therefore are critical for fundamental physiological processes such as muscle contraction, neuronal firing, and cellular homeostasis. As such, these ion-conducting proteins are subject to precise regulation...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28186506/epigenetic-regulation-of-hdac1-sumoylation-as-an-endogenous-neuroprotection-against-a%C3%AE-toxicity-in-a-mouse-model-of-alzheimer-s-disease
#12
Chih Chieh Tao, Wei Lun Hsu, Yun Li Ma, Sin Jhong Cheng, Eminy Hy Lee
Amyloid-β (Aβ) produces neurotoxicity in the brain and causes neuronal death, but the endogenous defense mechanism that is activated on Aβ insult is less well known. Here we found that acute Aβ increases the expression of PIAS1 and Mcl-1 via activation of MAPK/ERK, and Aβ induction of PIAS1 enhances HDAC1 SUMOylation in rat hippocampus. Knockdown of PIAS1 decreases endogenous HDAC1 SUMOylation and blocks Aβ induction of Mcl-1. Sumoylated HDAC1 reduces it association with CREB, increases CREB binding to the Mcl-1 promoter and mediates Aβ induction of Mcl-1 expression...
April 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28067168/sumoylation-in-neurological-diseases
#13
F-Y Liu, Y-F Liu, Y Yang, Z-W Luo, J-W Xiang, Z-G Chen, R-L Qi, T-H Yang, Y Xiao, W-J Qing, D W-C Li
Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases...
2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28029095/sumoylation-of-nav1-2-channels-mediates-the-early-response-to-acute-hypoxia-in-central-neurons
#14
Leigh D Plant, Jeremy D Marks, Steve An Goldstein
The mechanism for the earliest response of central neurons to hypoxia-an increase in voltage-gated sodium current (INa)-has been unknown. Here, we show that hypoxia activates the Small Ubiquitin-like Modifier (SUMO) pathway in rat cerebellar granule neurons (CGN) and that SUMOylation of NaV1.2 channels increases INa. The time-course for SUMOylation of single NaV1.2 channels at the cell surface and changes in INa coincide, and both are prevented by mutation of NaV1.2-Lys38 or application of a deSUMOylating enzyme...
December 28, 2016: ELife
https://www.readbyqxmd.com/read/27986376/bilateral-upregulation-of-%C3%AE-synuclein-expression-in-the-mouse-substantia-nigra-by-intracranial-rotenone-treatment
#15
Candace H Carriere, Na Hyea Kang, Lennard P Niles
The pesticide rotenone has been shown to cause systemic inhibition of mitochondrial complex I activity, with consequent degeneration of dopamine neurons along the nigrostriatal pathway, as observed in Parkinson's disease (PD). Recently, intracranial infusion of rotenone was found to increase the protein levels of the Lewy body constituents, α-synuclein and small ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse brain. These findings are supportive of a mouse model of PD, but information about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential marker of dopaminergic status, was not reported...
February 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27940916/hierarchical-crmp2-posttranslational-modifications-control-nav1-7-function
#16
Erik T Dustrude, Aubin Moutal, Xiaofang Yang, Yuying Wang, May Khanna, Rajesh Khanna
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27919694/neuron-specific-sumo-knockdown-suppresses-global-gene-expression-response-and-worsens-functional-outcome-after-transient-forebrain-ischemia-in-mice
#17
Lin Zhang, Xiaozhi Liu, Huaxin Sheng, Shuai Liu, Ying Li, Julia Q Zhao, David S Warner, Wulf Paschen, Wei Yang
Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) plays key roles in neurologic function in health and disease. Neuronal SUMOylation is essential for emotionality and cognition, and this pathway is dramatically activated in post-ischemic neurons, a neuroprotective response to ischemia. It is also known from cell culture studies that SUMOylation modulates gene expression. However, it remains unknown how SUMOylation regulates neuronal gene expression in vivo, in the physiologic state and after ischemia, and modulates post-ischemic recovery of neurologic function...
February 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/27882949/sumo-specific-protease-1-protects-neurons-from-apoptotic-death-during-transient-brain-ischemia-reperfusion
#18
Huijun Zhang, Yan Wang, Aoxue Zhu, Dehua Huang, Shining Deng, Jinke Cheng, Michael X Zhu, Yong Li
SUMO-specific protease 1 (SENP1) deconjugates SUMO from modified proteins. Although post-ischemic activation of SUMO conjugation was suggested to be neuroprotective against ischemia/reperfusion (I/R) injury, the function of SENP1 in this process remained unclear. Here we show that transient middle cerebral artery occlusion in mice followed by 6, 12 and 24 h reperfusion significantly enhanced SENP1 levels in the affected brain area, independent of transcription. Consistent with the increase in SENP1, the levels of SUMO1-conjugated proteins were decreased by I/R in cortical neurons of control littermate mice, but unchanged in that of animals with conditional ablation of SENP1 gene from adult principal neurons, the SENP1(flox/flox):CamKIIα-Cre (SENP1 cKO) mice...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27819299/several-posttranslational-modifications-act-in-concert-to-regulate-gephyrin-scaffolding-and-gabaergic-transmission
#19
Himanish Ghosh, Luca Auguadri, Sereina Battaglia, Zahra Simone Thirouin, Khaled Zemoura, Simon Messner, Mario A Acuña, Hendrik Wildner, Gonzalo E Yévenes, Andrea Dieter, Hiroshi Kawasaki, Michael O Hottiger, Hanns Ulrich Zeilhofer, Jean-Marc Fritschy, Shiva K Tyagarajan
GABAA receptors (GABAARs) mediate the majority of fast inhibitory neurotransmission in the brain via synergistic association with the postsynaptic scaffolding protein gephyrin and its interaction partners. However, unlike their counterparts at glutamatergic synapses, gephyrin and its binding partners lack canonical protein interaction motifs; hence, the molecular basis for gephyrin scaffolding has remained unclear. In this study, we identify and characterize two new posttranslational modifications of gephyrin, SUMOylation and acetylation...
November 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27747316/tyrosyl-dna-phosphodiesterase-i-a-critical-survival-factor-for-neuronal-development-and-homeostasis
#20
Robert C A M van Waardenburg
Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H(493)R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex...
2016: Journal of Neurology & Neuromedicine
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