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Leucine rich repeate kinase

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https://www.readbyqxmd.com/read/28104889/a-peptide-hormone-required-for-casparian-strip-diffusion-barrier-formation-in-arabidopsis-roots
#1
Takuya Nakayama, Hidefumi Shinohara, Mina Tanaka, Koki Baba, Mari Ogawa-Ohnishi, Yoshikatsu Matsubayashi
Plants achieve mineral ion homeostasis by means of a hydrophobic barrier on endodermal cells called the Casparian strip, which restricts lateral diffusion of ions between the root vascular bundles and the soil. We identified a family of sulfated peptides required for contiguous Casparian strip formation in Arabidopsis roots. These peptide hormones, which we named Casparian strip integrity factor 1 (CIF1) and CIF2, are expressed in the root stele and specifically bind the endodermis-expressed leucine-rich repeat receptor kinase GASSHO1 (GSO1)/SCHENGEN3 and its homolog, GSO2...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#2
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28090684/predict-pd-an-online-approach-to-prospectively-identify-risk-indicators-of-parkinson-s-disease
#3
Alastair J Noyce, Lea R'Bibo, Luisa Peress, Jonathan P Bestwick, Kerala L Adams-Carr, Niccolo E Mencacci, Christopher H Hawkes, Joseph M Masters, Nicholas Wood, John Hardy, Gavin Giovannoni, Andrew J Lees, Anette Schrag
BACKGROUND: A number of early features can precede the diagnosis of Parkinson's disease (PD). OBJECTIVE: To test an online, evidence-based algorithm to identify risk indicators of PD in the UK population. METHODS: Participants aged 60 to 80 years without PD completed an online survey and keyboard-tapping task annually over 3 years, and underwent smell tests and genotyping for glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) mutations...
January 16, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28071824/heart-rate-variability-in-leucine-rich-repeat-kinase-2-associated-parkinson-s-disease
#4
Naomi P Visanji, Grace S Bhudhikanok, Tiago A Mestre, Taneera Ghate, Kaviraj Udupa, Amaal AlDakheel, Barbara S Connolly, Carmen Gasca-Salas, Drew S Kern, Jennifer Jain, Elizabeth J Slow, Achinoam Faust-Socher, Sam Kim, Ruksana Azhu Valappil, Farah Kausar, Ekaterina Rogaeva, J William Langston, Caroline M Tanner, Birgitt Schüle, Anthony E Lang, Samuel M Goldman, Connie Marras
BACKGROUND: Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine-rich repeat kinase 2-associated PD. OBJECTIVES: This study investigated heart rate variability in LRRK2-associated PD. METHODS: Resting electrocardiograms were obtained from 20 individuals with LRRK2-associated PD, 37 nonmanifesting carriers, 48 related noncarriers, 26 idiopathic PD patients, and 32 controls...
January 10, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28041945/knockdown-transgenic-lrrk-drosophila-resists-paraquat-induced-locomotor-impairment-and-neurodegeneration-a-therapeutic-strategy-for-parkinson-s-disease
#5
Diana Quintero-Espinosa, Marlene Jimenez-Del-Rio, Carlos Velez-Pardo
Leucine-rich repeat kinase 2 (LRRK2) has been linked to familial and sporadic Parkinson's disease. However, it is still unresolved whether LRRK2 in dopaminergic (DAergic) neurons may or may not aggravate the phenotype. We demonstrate that knocking down (KD) the Lrrk gene by RNAi in DAergic neurons untreated or treated with paraquat (PQ) neither affected the number of DAergic clusters, tyrosine hydroxylase (TH) protein levels, lifespan nor locomotor activity when compared to control (i.e. TH/+) flies. KD transgenic Lrrk flies dramatically increased locomotor activity in presence of TH enzyme inhibitor alpha-methyl-para-tyrosine (aMT), whereas no effect on lifespan was observed in both fly lines...
December 29, 2016: Brain Research
https://www.readbyqxmd.com/read/28034752/the-nlrp3-inflammasome-and-bruton-s-tyrosine-kinase-in-platelets-co-regulate-platelet-activation-aggregation-and-in-vitro-thrombus-formation
#6
Pranav Murthy, Filip Durco, Jennifer L Miller-Ocuin, Teiko Takedai, Shruthi Shankar, Xiaoyan Liang, Xiao Liu, Xiangdong Cui, Ulka Sachdev, Dominik Rath, Michael T Lotze, Herbert J Zeh, Meinrad Gawaz, Alexander N Weber, Sebastian Vogel
Cleavage of interleukin-1β (IL-1β) is a key inflammatory event in immune cells and platelets, which is mediated by nucleotide-binding domain leucine rich repeat containing protein (NLRP3)-dependent activation of caspase-1. In immune cells, NLRP3 and caspase-1 form inflammasome complexes with the adaptor proteins apoptosis-associated speck-like protein containing a CARD (ASC) and bruton's tyrosine kinase (BTK). In platelets, however, the regulatory triggers and the functional effects of the NLRP3 inflammasome are unknown...
December 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28028237/nrf2-mitigates-lrrk2-and-%C3%AE-synuclein-induced-neurodegeneration-by-modulating-proteostasis
#7
Gaia Skibinski, Vicky Hwang, Dale Michael Ando, Aaron Daub, Alicia K Lee, Abinaya Ravisankar, Sara Modan, Mariel M Finucane, Benjamin A Shaby, Steven Finkbeiner
Mutations in leucine-rich repeat kinase 2 (LRRK2) and α-synuclein lead to Parkinson's disease (PD). Disruption of protein homeostasis is an emerging theme in PD pathogenesis, making mechanisms to reduce the accumulation of misfolded proteins an attractive therapeutic strategy. We determined if activating nuclear factor erythroid 2-related factor (Nrf2), a potential therapeutic target for neurodegeneration, could reduce PD-associated neuron toxicity by modulating the protein homeostasis network. Using a longitudinal imaging platform, we visualized the metabolism and location of mutant LRRK2 and α-synuclein in living neurons at the single-cell level...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28026097/barley-susceptibility-factor-racb-modulates-transcript-levels-of-signalling-protein-genes-in-compatible-interaction-with-blumeria-graminis-f-sp-hordei
#8
Vera Schnepf, A Corina Vlot, Karl Kugler, Ralph Hückelhoven
RHO (rat sarcoma homologue) GTPases are regulators of downstream transcriptional responses of eukaryotes to intracellular and extracellular stimuli. For plants, little is known about the function of Rho-like GTPases (called RACs [rat sarcoma-related C botulinum substrate] or ROPs [RHO of plants]) in transcriptional reprogramming of cells. However, in plant hormone response and innate immunity RAC/ROP proteins influence gene expression patterns. The barley RAC/ROP RACB is required for full susceptibility of barley to the powdery mildew fungus Blumeria graminis f...
December 27, 2016: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28003339/lrguk1-is-part-of-a-multiprotein-complex-required-for-manchette-function-and-male-fertility
#9
Hidenobu Okuda, Kathleen DeBoer, Anne E O'Connor, D Jo Merriner, Duangporn Jamsai, Moira K O'Bryan
Infertility occurs in 1 in 20 young men and is idiopathic in origin in most. We have reported that the leucine-rich repeat (LRR) and guanylate kinase-like domain containing, isoform (LRGUK)-1 is essential for sperm head shaping, via the manchette, and the initiation of sperm tail growth from the centriole/basal body, and thus, male fertility. Within this study we have used a yeast 2-hybrid screen of an adult testis library to identify LRGUK1-binding partners, which were then validated with a range of techniques...
December 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27995670/the-tomato-i-gene-for-fusarium-wilt-resistance-encodes-an-atypical-leucine-rich-repeat-receptor-like-protein-whose-function-is-nevertheless-dependent-on-sobir1-and-serk3-bak1
#10
Ann-Maree Catanzariti, Huong T T Do, Pierrick Bru, Mara de Sain, Louise F Thatcher, Martijn Rep, David A Jones
We have identified the tomato I gene for resistance to the Fusarium wilt fungus Fusarium oxysporum f. sp. lycopersici (Fol) and show that it encodes a membrane-anchored leucine-rich repeat receptor-like protein (LRR-RLP). Unlike most other LRR-RLP genes involved in plant defence, the I gene is not a member of a gene cluster and contains introns in its coding sequence. The I gene encodes a loopout domain larger than those in most other LRR-RLPs with a distinct composition rich in serine and threonine residues...
December 20, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27951586/nlrc3-is-an-inhibitory-sensor-of-pi3k-mtor-pathways-in-cancer
#11
Rajendra Karki, Si Ming Man, R K Subbarao Malireddi, Sannula Kesavardhana, Qifan Zhu, Amanda R Burton, Bhesh Raj Sharma, Xiaopeng Qi, Stephane Pelletier, Peter Vogel, Philip Rosenstiel, Thirumala-Devi Kanneganti
NLRs (nucleotide-binding domain and leucine-rich repeats) belong to a large family of cytoplasmic sensors that regulate an extraordinarily diverse range of biological functions. One of these functions is to contribute to immunity against infectious diseases, but dysregulation of their functional activity leads to the development of inflammatory and autoimmune diseases. Cytoplasmic innate immune sensors, including NLRs, are central regulators of intestinal homeostasis. NLRC3 (also known as CLR16.2 or NOD3) is a poorly characterized member of the NLR family and was identified in a genomic screen for genes encoding proteins bearing leucine-rich repeats (LRRs) and nucleotide-binding domains...
December 12, 2016: Nature
https://www.readbyqxmd.com/read/27943591/effects-of-lrrk2-inhibitors-on-nigrostriatal-dopaminergic-neurotransmission
#12
Qi Qin, Lian-Teng Zhi, Xian-Ting Li, Zhen-Yu Yue, Guo-Zhong Li, Hui Zhang
INTRODUCTION: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most prevalent cause of familial and sporadic Parkinson's disease (PD). Because most pathogenic LRRK2 mutations result in enhanced kinase activity, it suggests that LRRK2 inhibitors may serve as a potential treatment for PD. To evaluate whether LRRK2 inhibitors are effective therapies for PD, it is crucial to know whether LRRK2 inhibitors will affect dopaminergic (DAergic) neurotransmission. However, to date, there is no study to investigate the impact of LRRK2 inhibitors on DAergic neurotransmission...
December 9, 2016: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27939437/the-dual-enzyme-lrrk2-hydrolyzes-gtp-in-both-its-gtpase-and-kinase-domains-in-vitro
#13
Zhiyong Liu, Andrew B West
The evolutionarily conserved enzyme encoded by the leucine-rich repeat kinase 2 gene, LRRK2, harbors both a Rab-like GTPase domain and a serine/threonine protein kinase domain. Pathogenic mutations in either the GTPase or kinase domain can cause neurodegeneration and Parkinson disease. No high-resolution structure of the human LRRK2 kinase domain is available but the most common mutation, G2019S in the kinase domain, is predicted to alter the ATP-binding pocket structure and interaction with divalent cations...
December 8, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27925204/rabs-membrane-dynamics-and-parkinson-s-disease
#14
REVIEW
Bor Luen Tang
Genes encoding cellular membrane trafficking components, namely RAB7L1 and RAB39B, are more recently recognized factors associated with Parkinson's disease (PD). Encoded by a gene within the PARK16 locus, RAB7L1 interacts with Leucine-rich repeat kinase 2 (LRRK2) to act in intracellular transport processes that are likely important for neuronal survival and function. LRRK2 also directly phosphorylates a number of other Rab proteins. On the other hand, nonsense and missense mutations of the X-chromosome localized RAB39B were shown to underlie X-linked intellectual disability (ID) in male patients with early-onset PD...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27923613/an-arabidopsis-thaliana-receptor-dead-kinase1-rdk1-gene-functions-as-a-positive-regulator-in-plant-responses-to-aba
#15
Dhinesh Kumar, Ritesh Kumar, Dongwon Baek, Tae-Kyung Hyun, Woo Sik Chung, Dae-Jin Yun, Jae-Yean Kim
Abscisic acid (ABA) is a major phytohormone involved in important stress-related and developmental plant processes. Membrane-delimited ABA signal transduction plays an important role in early ABA signaling, but the molecular mechanisms connecting core signaling components to the plasma membrane (PM) are unclear. Plants have evolved a large number of receptor-like kinases (RLKs) to modulate diverse biological processes by perceiving extracellular stimuli and activating downstream signaling responses. Here, a putative leucine-rich repeat (LRR)-RLK gene named RECEPTOR DEAD KINASE1 (AtRDK1) was identified and characterized in Arabidopsis thaliana...
December 3, 2016: Molecular Plant
https://www.readbyqxmd.com/read/27920157/two-serk-receptor-like-kinases-interact-with-ems1-to-control-anther-cell-fate-determination
#16
Zhiyong Li, Yao Wang, Jian Huang, Nagib Ahsan, Gabriel Biener, Joel Paprocki, Jay J Thelen, Valerica Raicu, Dazhong Zhao
Cell signaling pathways mediated by leucine-rich repeat receptor-like kinases (LRR-RLKs) are essential for plant growth, development, and defense. The EMS1 (EXCESS MICROSPOROCYTES1) LRR-RLK and its small protein ligand TPD1 (TAPETUM DETERMINANT1) play a fundamental role in somatic and reproductive cell differentiation during early anther development in Arabidopsis (Arabidopsis thaliana). However, it is unclear whether other cell surface molecules serve as coregulators of EMS1. Here, we show that SERK1 (SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASE1) and SERK2 LRR-RLKs act redundantly as coregulatory and physical partners of EMS1...
January 2017: Plant Physiology
https://www.readbyqxmd.com/read/27914807/phosphorylation-of-p53-by-lrrk2-induces-microglial-tumor-necrosis-factor-%C3%AE-mediated-neurotoxicity
#17
Dong Hwan Ho, Wongi Seol, Jin Hwan Eun, Il-Hong Son
Leucine-rich repeat kinase (LRRK2), a major causal gene of Parkinson's disease (PD), functions as a kinase. The most prevalent mutation of LRRK2 is G2019S. It exhibits increased kinase activity compared to the wildtype LRRK2. Previous studies have shown that LRRK2 can phosphorylate p53 at T304 and T377 of threonine-X-arginine (TXR) motif in neurons. Reduction of LRRK2 expression or inhibition of LRRK2 kinase activity has been shown to be able to alleviate LPS-induced neuroinflammation in microglia cells. In this study, we found that LRRK2 could also phosphorylate p53 in microglia model BV2 cells...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913672/first-model-of-dimeric-lrrk2-the-challenge-of-unrevealing-the-structure-of-a-multidomain-parkinson-s-associated-protein
#18
REVIEW
Giambattista Guaitoli, Bernd K Gilsbach, Francesco Raimondi, Christian Johannes Gloeckner
Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene represent the most common cause of Mendelian forms of Parkinson's disease, among autosomal dominant cases. Its gene product, LRRK2, is a large multidomain protein that belongs to the Roco protein family exhibiting GTPase and kinase activity, with the latter activity increased by pathogenic mutations. To allow rational drug design against LRRK2 and to understand the cross-regulation of the G- and the kinase domain at a molecular level, it is key to solve the three-dimensional structure of the protein...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913671/l-rrk-de-triomphe-a-solution-for-lrrk2-gtpase-activity
#19
REVIEW
Jonathon Nixon-Abell, Daniel C Berwick, Kirsten Harvey
Leucine-rich repeat kinase 2 (LRRK2) is a central protein in the pathogenesis of Parkinson's disease (PD), yet its normal function has proved stubbornly hard to elucidate. Even though it remains unclear how pathogenic mutations affect LRRK2 to cause PD, recent findings provide increasing cause for optimism. We summarise here the developing consensus over the effect of pathogenic mutations in the Ras of complex proteins and C-terminal of Roc domains on LRRK2 GTPase activity. This body of work has been greatly reinforced by our own study of the protective R1398H variant contained within the LRRK2 GTPase domain...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27913670/screening-for-chemical-modulators-for-lrrk2
#20
REVIEW
Heather Mortiboys
After the discovery of leucine-rich repeat kinase 2 (LRRK2) as a risk factor for sporadic Parkinson's disease (PD) and mutations in LRRK2 as a cause of some forms of familial PD, there has been substantial interest in finding chemical modulators of LRRK2 function. Most of the pathogenic mutations in LRRK2 are within the enzymatic cores of the protein; therefore, many screens have focused on finding chemical modulators of this enzymatic activity. There are alternative screening approaches that could be taken to investigate compounds that modulate LRRK2 cellular functions...
December 15, 2016: Biochemical Society Transactions
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