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Leucine rich repeate kinase

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https://www.readbyqxmd.com/read/29346521/the-intracellular-and-intercellular-cross-talk-during-subsidiary-cell-formation-in-zea-mays-existing-and-novel-components-orchestrating-cell-polarization-and-asymmetric-division
#1
P Apostolakos, P Livanos, E Giannoutsou, E Panteris, B Galatis
Background: Formation of stomatal complexes in Poaceae is the outcome of three asymmetric and one symmetric cell division occurring in particular leaf protodermal cells. In this definite sequence of cell division events, the generation of subsidiary cells is of particular importance and constitutes an attractive model for studying local intercellular stimulation. In brief, an induction stimulus emitted by the guard cell mother cells (GMCs) triggers a series of polarization events in their laterally adjacent protodermal cells...
January 15, 2018: Annals of Botany
https://www.readbyqxmd.com/read/29336357/distinctive-roles-of-rac1-and-rab29-in-lrrk2-mediatedmembrane-trafficking-and-neurite-outgrowth
#2
Min Feng, Xin Hu, Na Li, Fan Hu, Fei Chang, Hong-Fei Xu, Yong-Jian Liu
Parkinson's disease (PD) associated leucine-rich repeat kinase 2 (LRRK2) mutants have shown pathogenic effects on variety of subcellular processes.Two small GTPases Rac1 and Rab29 have been indicated as possible downstream effectors participating in LRRK2 signaling but their detail mechanisms remain unclear. In this study, we have used biochemical and cell biology approaches to address whether two GTPases interact with LRRK2 and hence function differently in LRRK2 mediated pathogenesis.Here we show thatRac1 and Rab29 specifically interact with LRRK2with higher affinity for Rab29and with different preference in functional domain binding...
November 1, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/29320478/an-extracellular-network-of-arabidopsis-leucine-rich-repeat-receptor-kinases
#3
Elwira Smakowska-Luzan, G Adam Mott, Katarzyna Parys, Martin Stegmann, Timothy C Howton, Mehdi Layeghifard, Jana Neuhold, Anita Lehner, Jixiang Kong, Karin Grünwald, Natascha Weinberger, Santosh B Satbhai, Dominik Mayer, Wolfgang Busch, Mathias Madalinski, Peggy Stolt-Bergner, Nicholas J Provart, M Shahid Mukhtar, Cyril Zipfel, Darrell Desveaux, David S Guttman, Youssef Belkhadir
The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions...
January 10, 2018: Nature
https://www.readbyqxmd.com/read/29317492/a-protein-interaction-network-centered-on-leucine-rich-repeats-and-immunoglobulin-like-domains-1-lrig1-regulates-growth-factor-receptors
#4
Mahmood Faraz, Carl Herdenberg, Camilla Holmlund, Roger Henriksson, Håkan Hedman
Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases (RTKs). The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates RTKs remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor alpha (PDGFRA), LRIG1, and shRNAs against the identified LRIG1 interactors...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#5
REVIEW
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
https://www.readbyqxmd.com/read/29315801/the-emerging-role-of-rab-gtpases-in-the-pathogenesis-of-parkinson-s-disease
#6
REVIEW
Yujing Gao, Gabrielle R Wilson, Sarah E M Stephenson, Kiymet Bozaoglu, Matthew J Farrer, Paul J Lockhart
The identification of pathogenic mutations in Ras analog in brain 39B (RAB39B) and Ras analog in brain 32 (RAB32) that cause Parkinson's disease (PD) has highlighted the emerging role of protein trafficking in disease pathogenesis. Ras analog in brain (Rab) Guanosine triphosphatase (GTPase) function as master regulators of membrane trafficking, including vesicle formation, movement along cytoskeletal networks, and membrane fusion. Recent studies have linked Rab GTPases with α-synuclein, Leucine-rich repeat kinase 2, and Vacuolar protein sorting 35, 3 key proteins in PD pathogenesis...
January 9, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29315334/immune-related-genetic-enrichment-in-frontotemporal-dementia-an-analysis-of-genome-wide-association-studies
#7
Iris Broce, Celeste M Karch, Natalie Wen, Chun C Fan, Yunpeng Wang, Chin Hong Tan, Naomi Kouri, Owen A Ross, Günter U Höglinger, Ulrich Muller, John Hardy, Parastoo Momeni, Christopher P Hess, William P Dillon, Zachary A Miller, Luke W Bonham, Gil D Rabinovici, Howard J Rosen, Gerard D Schellenberg, Andre Franke, Tom H Karlsen, Jan H Veldink, Raffaele Ferrari, Jennifer S Yokoyama, Bruce L Miller, Ole A Andreassen, Anders M Dale, Rahul S Desikan, Leo P Sugrue
BACKGROUND: Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. METHODS AND FINDINGS: Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis...
January 2018: PLoS Medicine
https://www.readbyqxmd.com/read/29305532/lrrk2-g2019s-induces-anxiety-depression-like-behavior-prior-to-the-onset-of-motor-dysfunction-with-5-ht1a-receptor-upregulation-in-mice
#8
Juhee Lim, Yeojin Bang, Jong-Hyun Choi, Arum Han, Min-Soo Kwon, Kwang Hyeon Liu, Hyun Jin Choi
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD). The neuropathology of LRRK2 mutation-related PD is indistinguishable from that of idiopathic PD, including increased dopaminergic neurodegeneration and Lewy bodies, but its subtle non-motor phenotypes have not been fully evaluated. In the present study, we examined anxiety/depression-like behaviors and accompanying neurochemical changes in differently aged transgenic (Tg) mice expressing human mutant LRRK2 G2019S...
January 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29305429/back-to-the-future-new-target-validated-rab-antibodies-for-evaluating-lrrk2-signalling-in-cell-biology-and-parkinson-s-disease
#9
Patrick A Eyers
The addition of phosphate groups to substrates allows protein kinases to regulate a myriad of biological processes, and contextual analysis of protein-bound phosphate is important for understanding how kinases contribute to physiology and disease. Leucine-rich repeat kinase 2 (LRRK2) is a Ser/Thr kinase linked to familial and sporadic cases of Parkinson's disease (PD). Recent work established that multiple Rab GTPases are physiological substrates of LRRK2, with Rab10 in particular emerging as a human substrate whose site-specific phosphorylation mirrors hyperactive LRRK2 lesions associated with PD...
January 5, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29286425/rab10-phosphorylation-detection-by-lrrk2-activity-using-sds-page-with-a-phosphate-binding-tag
#10
Genta Ito, Taisuke Tomita
Mutations in leucine-rich repeat kinase 2 (LRRK2) have been shown to be linked with familial Parkinson's disease (FPD). Since abnormal activation of the kinase activity of LRRK2 has been implicated in the pathogenesis of PD, it is essential to establish a method to evaluate the physiological levels of the kinase activity of LRRK2. Recent studies revealed that LRRK2 phosphorylates members of the Rab GTPase family, including Rab10, under physiological conditions. Although the phosphorylation of endogenous Rab10 by LRRK2 in cultured cells could be detected by mass spectrometry, it has been difficult to detect it by immunoblotting due to the poor sensitivity of currently available phosphorylation-specific antibodies for Rab10...
December 14, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29247303/root-cone-angle-is-enlarged-in-docs1-lrr-rlk-mutants-in-rice
#11
M Bettembourg, M Dal-Soglio, C Bureau, A Vernet, A Dardoux, M Portefaix, M Bes, D Meynard, D Mieulet, B Cayrol, C Perin, B Courtois, J F Ma, A Dievart
BACKGROUND: The DEFECTIVE IN OUTER CELL LAYER SPECIFICATION 1 (DOCS1) gene belongs to the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) subfamily. It has been discovered few years ago in Oryza sativa (rice) in a screen to isolate mutants with defects in sensitivity to aluminum. The c68 (docs1-1) mutant possessed a nonsense mutation in the C-terminal part of the DOCS1 kinase domain. FINDINGS: We have generated a new loss-of-function mutation in the DOCS1 gene (docs1-2) using the CRISPR-Cas9 technology...
December 15, 2017: Rice
https://www.readbyqxmd.com/read/29246624/lrig-proteins-in-glioma-functional-roles-molecular-mechanisms-and-potential-clinical-implications
#12
REVIEW
Feng Mao, Baofeng Wang, Qungen Xiao, Fangling Cheng, Ting Lei, Dongsheng Guo
Gliomas are the most common intracranial tumors of the nervous system. These tumors are characterized by unlimited cell proliferation and excessive invasiveness. Despite the advances in diagnostic imaging, microneurosurgical techniques, radiation therapy, and chemotherapy, significant increases in the progression free survival of glioma patients have not been achieved. Improvements in our understanding of the molecular subtypes of gliomas and the underlying alterations in specific signaling pathways may impact both the diagnosis and the treatment strategies for patients with gliomas...
December 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29242232/ralf4-19-peptides-interact-with-lrx-proteins-to-control-pollen-tube-growth-in-arabidopsis
#13
Martin A Mecchia, Gorka Santos-Fernandez, Nadine N Duss, Sofía C Somoza, Aurélien Boisson-Dernier, Valeria Gagliardini, Andrea Martínez-Bernardini, Tohnyui Ndinyanka Fabrice, Christoph Ringli, Jorge P Muschietti, Ueli Grossniklaus
The communication of changes in the extracellular matrix to the interior of the cell is crucial for a cell's function. The extracellular peptides of the RAPID ALKALINIZATION FACTOR (RALF) family have been identified as ligands of receptor-like kinases of the CrRLK1L subclass, but the exact mechanism of their perception is unclear. We found that Arabidopsis RALF4 and RALF19 redundantly regulate pollen tube integrity and growth, and that their function depends on pollen-expressed proteins of the LEUCINE-RICH REPEAT EXTENSIN (LRX) family, which play a role in cell wall development but whose mode of action is not understood...
December 14, 2017: Science
https://www.readbyqxmd.com/read/29241968/case-control-analysis-of-leucine-rich-repeat-kinase-2-protective-variants-in-alzheimer-s-disease
#14
Adeline S L Ng, Ebonne Y L Ng, Yi Jayne Tan, Nagaendran Kandiah, Juan Zhou, Shahul Hameed, Simon K S Ting, Eng-King Tan
Amyloid is the main pathological substrate of Alzheimer's disease (AD) and has been described in leucine-rich repeat kinase 2 (LRRK2) carriers with Parkinson's disease. LRRK2 has been linked with amyloid precursor protein pathways in neurodegeneration. Two common LRRK2 variants, R1398H and N551K, have been shown to be protective in multiple Parkinson's disease cohorts. We hypothesized that R1398H and N551K may be protective in AD. In a case-control study involving 1390 subjects (719 controls and 671 AD cases), R1398H was demonstrated in 16...
November 27, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29231777/de-novo-transcriptome-study-identifies-candidate-genes-involved-in-resistance-to-austropuccinia-psidii-myrtle-rust-in-syzygium-luehmannnii-riberry
#15
Peri Ann Tobias, David Guest, Carsten Külheim, Robert F Park
Austropuccinia psidii, causal agent of myrtle rust, was discovered in Australia in 2010 and has since become established on a wide range of species within the Myrtaceae. Syzygium luehmannii, endemic to Australia, is an increasingly valuable berry crop. Plants were screened for responses to A. psidii inoculation and specific resistance, in the form of localised necrosis, was determined in 29% of individuals. To understand the molecular basis underlying this response, mRNA was sequenced from leaf samples taken pre-inoculation, and at 24 and 48 hours post inoculation, from four resistant and four susceptible plants...
December 12, 2017: Phytopathology
https://www.readbyqxmd.com/read/29230231/activation-of-the-lrr-receptor-like-kinase-psy1r-requires-transphosphorylation-of-residues-in-the-activation-loop
#16
Christian B Oehlenschlæger, Lotte B A Gersby, Nagib Ahsan, Jesper T Pedersen, Astrid Kristensen, Tsvetelina V Solakova, Jay J Thelen, Anja T Fuglsang
PSY1R is a leucine-rich repeat (LRR) receptor-like kinase (RLK) previously shown to act as receptor for the plant peptide hormone PSY1 (peptide containing sulfated tyrosine 1) and to regulate cell expansion. PSY1R phosphorylates and thereby regulates the activity of plasma membrane-localized H+-ATPases. While this mechanism has been studied in detail, little is known about how PSY1R itself is activated. Here we studied the activation mechanism of PSY1R. We show that full-length PSY1R interacts with members of the SERK co-receptor family in planta...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29223392/parkinson-s-disease-associated-mutant-lrrk2-phosphorylates-rab7l1-and-modifies-trans-golgi-morphology
#17
Tetta Fujimoto, Tomoki Kuwahara, Tomoya Eguchi, Maria Sakurai, Tadayuki Komori, Takeshi Iwatsubo
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the major genetic cause of autosomal-dominantly inherited Parkinson's disease. LRRK2 is implicated in the regulation of intracellular trafficking, neurite outgrowth and PD risk in connection with Rab7L1, a putative interactor of LRRK2. Recently, a subset of Rab GTPases have been reported as substrates of LRRK2. Here we examine the kinase activity of LRRK2 on Rab7L1 in situ in cells. Phos-tag analyses and metabolic labeling assays revealed that LRRK2 readily phosphorylates Golgi-localized wild-type Rab7L1 but not mutant forms that are distributed in the cytoplasm...
December 6, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29213277/functional-and-structural-characterization-of-a-receptor-like-kinase-involved-in-germination-and-cell-expansion-in-arabidopsis
#18
Zhen Wu, Shan Liang, Wen Song, Guangzhong Lin, Weiguang Wang, Heqiao Zhang, Zhifu Han, Jijie Chai
Leucine-rich repeat receptor-like kinases (LRR-RLKs) are widespread in different plant species and play important roles in growth and development. Germination inhibition is vital for the completion of seed maturation and cell expansion is a fundamental cellular process driving plant growth. Here, we report genetic and structural characterizations of a functionally uncharacterized LRR-RLK, named GRACE (Germination Repression and Cell Expansion receptor-like kinase). Overexpression of GRACE in Arabidopsis exhibited delayed germination, enlarged cotyledons, rosette leaves and stubbier petioles...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29190504/phytohormone-priming-elevates-the-accumulation-of-defense-related-gene-transcripts-and-enhances-bacterial-blight-disease-resistance-in-cassava
#19
Sunisa Yoodee, Yohko Kobayashi, Wisuwat Songnuan, Chuenchit Boonchird, Siripong Thitamadee, Issei Kobayashi, Jarunya Narangajavana
Cassava bacterial blight (CBB) disease caused by Xanthomonas axonopodis pv. manihotis (Xam) is a severe disease in cassava worldwide. In addition to causing significant cassava yield loss, CBB disease has not been extensively studied, especially in terms of CBB resistance genes. The present research demonstrated the molecular mechanisms underlining the defense response during Xam infection in two cassava cultivars exhibiting different degrees of disease resistance, Huay Bong60 (HB60) and Hanatee (HN). Based on gene expression analysis, ten of twelve putative defense-related genes including, leucine-rich repeat receptor-like kinases (LRR-RLKs), resistance (R), WRKY and pathogenesis-related (PR) genes, were differentially expressed between these two cassava cultivars during Xam infection...
November 27, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/29166931/elevated-lrrk2-autophosphorylation-in-brain-derived-and-peripheral-exosomes-in-lrrk2-mutation-carriers
#20
Shijie Wang, Zhiyong Liu, Tao Ye, Omar S Mabrouk, Tyler Maltbie, Jan Aasly, Andrew B West
Missense mutations in the leucine-rich repeat kinase 2 (LRRK2) gene can cause late-onset Parkinson disease (PD). LRRK2 mutations increase LRRK2 kinase activities that may increase levels of LRRK2 autophosphorylation at serine 1292 (pS1292) and neurotoxicity in model systems. pS1292-LRRK2 protein can be packaged into exosomes and measured in biobanked urine. Herein we provide evidence that pS1292-LRRK2 protein is robustly expressed in cerebral spinal fluid (CSF) exosomes. In a novel cohort of Norwegian subjects with and without the G2019S-LRRK2 mutation, with and without PD, we quantified levels of pS1292-LRRK2, total LRRK2, and other exosome proteins in urine from 132 subjects and in CSF from 82 subjects...
November 22, 2017: Acta Neuropathologica Communications
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