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Leucine rich repeate kinase

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https://www.readbyqxmd.com/read/28424707/new-insights-on-leucine-rich-repeats-receptor-like-kinase-orthologous-relationships-in-angiosperms
#1
Jean-François Dufayard, Mathilde Bettembourg, Iris Fischer, Gaetan Droc, Emmanuel Guiderdoni, Christophe Périn, Nathalie Chantret, Anne Diévart
Leucine-Rich Repeats Receptor-Like Kinase (LRR-RLK) genes represent a large and complex gene family in plants, mainly involved in development and stress responses. These receptors are composed of an LRR-containing extracellular domain (ECD), a transmembrane domain (TM) and an intracellular kinase domain (KD). To provide new perspectives on functional analyses of these genes in model and non-model plant species, we performed a phylogenetic analysis on 8,360 LRR-RLK receptors in 31 angiosperm genomes (8 monocots and 23 dicots)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28420983/increased-oxidative-stress-markers-in-cerebrospinal-fluid-from-healthy-subjects-with-parkinson-s-disease-associated-lrrk2-gene-mutations
#2
David A Loeffler, Andrea C Klaver, Mary P Coffey, Jan O Aasly, Peter A LeWitt
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of inherited Parkinson's disease (PD). The most common PD-associated LRRK2 mutation, G2019S, induces increased production of reactive oxygen species in vitro. We therefore hypothesized that individuals with PD-associated LRRK2 mutations might have increased concentrations of oxidative stress markers and/or decreased total antioxidant capacity (TAC) in their cerebrospinal fluid (CSF). We measured two oxidative stress markers, namely 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), and TAC in CSF from LRRK2 mutation-bearing PD patients (LRRK2 PD = 19), sporadic PD patients (sPD = 31), and healthy control subjects with or without these mutations (LRRK2 CTL = 30, CTL = 27)...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28417442/mechanisms-of-gene-environment-interactions-in-parkinson-s-disease
#3
REVIEW
Sheila M Fleming
PURPOSE OF REVIEW: The purpose of the study was to discuss the main mechanisms associated with environmental and genetic factors that contribute to the development of Parkinson's disease (PD). RECENT FINDINGS: Novel genetic contributors to PD are being identified at a rapid pace in addition to novel environmental factors. The discovery of mutations in alpha-synuclein and leucine-rich repeat kinase 2 causing inherited forms of PD along with epidemiological, in vitro, and in vivo studies identifying herbicides, pesticides, and metals as risk factors have dramatically improved our understanding of mechanisms involved in the development of PD...
April 17, 2017: Current Environmental Health Reports
https://www.readbyqxmd.com/read/28409271/unique-presentation-of-cutis-laxa-with-leigh-like-syndrome-due-to-echs1-deficiency
#4
S Balasubramaniam, L G Riley, D Bratkovic, D Ketteridge, N Manton, M J Cowley, V Gayevskiy, T Roscioli, M Mohamed, T Gardeitchik, E Morava, J Christodoulou
Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade...
April 13, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28408707/admixture-mapping-of-subclinical-atherosclerosis-and-subsequent-clinical-events-among-african-americans-in-2-large-cohort-studies
#5
Aditi Shendre, Howard Wiener, Marguerite R Irvin, Degui Zhi, Nita A Limdi, Edgar T Overton, Christina L Wassel, Jasmin Divers, Jerome I Rotter, Wendy S Post, Sadeep Shrestha
BACKGROUND: Local ancestry may contribute to the disproportionate burden of subclinical and clinical cardiovascular disease among admixed African Americans compared with other populations, suggesting a rationale for admixture mapping. METHODS AND RESULTS: We estimated local European ancestry (LEA) using Local Ancestry inference in adMixed Populations using Linkage Disequilibrium method (LAMP-LD) and evaluated the association with common carotid artery intima-media thickness (cCIMT) using multivariable linear regression analysis among 1554 African Americans from MESA (Multi-Ethnic Study of Atherosclerosis)...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28406987/arabidopsis-leucine-rich-repeat-receptor-like-kinase-nilr1-is-required-for-induction-of-innate-immunity-to-parasitic-nematodes
#6
Badou Mendy, Mary Wanjiku Wang'ombe, Zoran S Radakovic, Julia Holbein, Muhammad Ilyas, Divykriti Chopra, Nick Holton, Cyril Zipfel, Florian M W Grundler, Shahid Siddique
Plant-parasitic nematodes are destructive pests causing losses of billions of dollars annually. An effective plant defence against pathogens relies on the recognition of pathogen-associated molecular patterns (PAMPs) by surface-localised receptors leading to the activation of PAMP-triggered immunity (PTI). Extensive studies have been conducted to characterise the role of PTI in various models of plant-pathogen interactions. However, far less is known about the role of PTI in roots in general and in plant-nematode interactions in particular...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28384649/differential-cle-peptide-perception-by-plant-receptors-implicated-from-structural-and-functional-analyses-of-tdif-tdr-interactions
#7
Zhijie Li, Sayan Chakraborty, Guozhou Xu
Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells...
2017: PloS One
https://www.readbyqxmd.com/read/28383562/vps35-regulates-parkin-substrate-aimp2-toxicity-by-facilitating-lysosomal-clearance-of-aimp2
#8
Seung Pil Yun, Hyojung Kim, Sangwoo Ham, Seung-Hwan Kwon, Gum Hwa Lee, Joo-Ho Shin, Sang Hun Lee, Han Seok Ko, Yunjong Lee
Vacuolar protein sorting-associated protein 35 (VPS35) is involved in retrograde transport of proteins from endosomes to trans-Golgi network. Gene mutations in VPS35 are linked to autosomal dominant late-onset Parkinson's disease (PD). Although the identification of VPS35 mutations has provided novel insight about its interactions with several PD-associated genes including leucine-rich repeat kinase 2 (LRRK2) and α-synuclein, little information is available about the molecular mechanisms of cell death downstream of VPS35 dysfunction...
April 6, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28370517/the-prodromal-phase-of-leucine-rich-repeat-kinase-2-associated-parkinson-disease-clinical-and-imaging-studies
#9
Claustre Pont-Sunyer, Eduardo Tolosa, Chelsea Caspell-Garcia, Christopher Coffey, Roy N Alcalay, Piu Chan, John E Duda, Maurizio Facheris, Rubén Fernández-Santiago, Kenneth Marek, Francisco Lomeña, Connie Marras, Elisabet Mondragon, Rachel Saunders-Pullman, Bjorg Waro
BACKGROUND: Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD. OBJECTIVES: To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers. METHODS: A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated...
March 28, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28369573/translatome-analysis-of-an-nb-lrr-immune-response-identifies-important-contributors-to-plant-immunity-in-arabidopsis
#10
Louis-Valentin Meteignier, Mohamed El Oirdi, Mathias Cohen, Teura Barff, Dominick Matteau, Jean-François Lucier, Sébastien Rodrigue, Pierre-Etienne Jacques, Keiko Yoshioka, Peter Moffett
An important branch of plant immunity involves the recognition of pathogens by nucleotide-binding, leucine-rich repeat (NB-LRR) proteins. However, signaling events downstream of NB-LRR activation are poorly understood. We have analysed the Arabidopsis translatome using ribosome affinity purification and RNA sequencing. Our results show that the translational status of hundreds of transcripts is differentially affected upon activation of the NB-LRR protein RPM1, showing an overall pattern of a switch away from growth-related activities to defense...
March 28, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28368449/genome-wide-sequencing-of-longan-dimocarpus-longan-lour-provides-insights-into-molecular-basis-of-its-polyphenol-rich-characteristics
#11
YuLing Lin, JiuMeng Min, RuiLian Lai, ZhangYan Wu, YuKun Chen, LiLi Yu, ChunZhen Cheng, YuanChun Jin, QiLin Tian, QingFeng Liu, WeiHua Liu, ChengGuang Zhang, LiXia Lin, Yan Hu, DongMin Zhang, MinKyaw Thu, ZiHao Zhang, ShengCai Liu, ChunShui Zhong, XiaoDong Fang, Jian Wang, Huanming Yang, Rajeev K Varshney, Ye Yin, ZhongXiong Lai
Background: Longan ( Dimocarpus longan Lour.), an important subtropical fruit in the family Sapindaceae , is grown in more than ten countries. Longan is an edible drupe fruit and a source of traditional medicine with polyphenol-rich traits. Tree size, alternate bearing, and witches' broom disease still pose serious problems. To gain insights into the genomic basis of longan traits, a draft genome sequence was assembled. Results: The draft genome (about 471.88 Mb) of a China longan cultivar, 'Honghezi', was estimated to contain 31,007 genes and 261...
March 28, 2017: GigaScience
https://www.readbyqxmd.com/read/28353288/small-molecule-inhibitors-of-lrrk2
#12
John M Hatcher, Hwan Geun Choi, Dario R Alessi, Nathanael S Gray
Mutations in the leucine-rich repeat kinase 2 (LRRK2) protein have been genetically and functionally linked to Parkinson's disease (PD). The kinase activity of LRRK2 is increased by pathogenic mutations; therefore, modulation of LRRK2 kinase activity by a selective small-molecule inhibitor has been proposed as a potentially viable treatment for Parkinson's disease. This chapter presents a historical overview of the development and bioactivity of several small-molecule LRRK2 inhibitors that have been used to inhibit LRRK2 kinase activity in vitro or in vivo...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353285/lrrk2-and-the-lrrktosome-at-the-crossroads-of-programmed-cell-death-clues-from-rip-kinase-relatives
#13
Hardy J Rideout, Diane B Re
Since its cloning and identification in 2004, considerable gains have been made in the understanding of the basic functionality of leucine-rich repeat kinase 2 (LRRK2), including its kinase and GTPase activities, its protein interactors and subcellular localization, and its expression in the CNS and peripheral tissues. However, the mechanism(s) by which expression of mutant forms of LRRK2 lead to the death of dopaminergic neurons of the ventral midbrain remains largely uncharacterized. Because of its complex domain structure, LRRK2 exhibits similarities with multiple protein families including ROCO proteins, as well as the RIP kinases...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353284/models-of-lrrk2-associated-parkinson-s-disease
#14
Yulan Xiong, Ted M Dawson, Valina L Dawson
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic causes of Parkinson's disease (PD) and also one of the strongest genetic risk factors in sporadic PD. The LRRK2 protein contains a GTPase and a kinase domain and several protein-protein interaction domains. Both in vitro and in vivo assays in different model systems have provided tremendous insights into the molecular mechanisms underlying LRRK2-induced dopaminergic neurodegeneration. Among all the model systems, animal models are crucial tools to study the pathogenesis of human disease...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353282/lrrk2-and-the-immune-system
#15
Nicolas L Dzamko
Polymorphisms in leucine-rich repeat kinase 2 (LRRK2) have been linked to familial Parkinson's disease, increased risk of sporadic Parkinson's disease, increased risk of Crohn's inflammatory bowel disease, and increased susceptibility to leprosy. As well as LRRK2 mutations, these diseases share in common immune dysfunction and inflammation. LRRK2 is highly expressed in particular immune cells and has been biochemically linked to the intertwined pathways regulating inflammation, mitochondrial function, and autophagy/lysosomal function...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353281/molecular-insights-and-functional-implication-of-lrrk2-dimerization
#16
Laura Civiero, Isabella Russo, Luigi Bubacco, Elisa Greggio
The Parkinson's disease protein leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein with an enzymatic core comprising serine-threonine kinase and GTPase activities and a number of protein-protein interaction domains. While the complex domain architecture of LRRK2 has hampered its structural investigation, there is convincing evidence that LRRK2 can form dimers in solution and in the cell and that the GTPase/ROC domain plays a central role in this process. This chapter focuses on recent studies addressing the molecular nature, the functional significance, and the pathological implication of LRRK2 dimerization...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353280/lrrk2-and-autophagy
#17
Claudia Manzoni, Patrick A Lewis
Leucine-rich repeat kinase 2 (LRRK2) has been implicated in a wide range of cellular processes, including the catabolic pathways collectively described as autophagy. In this chapter, the evidence linking LRRK2 to autophagy will be examined, along with how regulation of autophagy and lysosomal pathways may provide a nexus between the physiological function of this protein and the different diseases with which it has been associated. Data from cellular and animal models for LRRK2 function and dysfunction support a role in the regulation and control of autophagic pathways in the cell, although the extant results do not provide a clear indication as to whether LRRK2 is a positive or negative regulator of these pathways, and there are conflicting data as to the impact of mutations in LRRK2 causative for Parkinson's disease...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353279/understanding-the-gtpase-activity-of-lrrk2-regulation-function-and-neurotoxicity
#18
An Phu Tran Nguyen, Darren J Moore
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most frequent cause of Parkinson's disease (PD) with late-onset and autosomal-dominant inheritance. LRRK2 belongs to the ROCO superfamily of proteins, characterized by a Ras-of-complex (Roc) GTPase domain in tandem with a C-terminal-of-Roc (COR) domain. LRRK2 also contains a protein kinase domain adjacent to the Roc-COR tandem domain in addition to multiple repeat domains. Disease-causing familial mutations cluster within the Roc-COR tandem and kinase domains of LRRK2, where they act to either impair GTPase activity or enhance kinase activity...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353278/lrrk2-phosphorylation
#19
R Jeremy Nichols
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene were discovered in 2004 and have been found to be the most frequently mutated gene in Parkinson's disease. LRRK2 is a large multi-domain protein with a functional GTPase and kinase domain. The signal transduction pathways in which LRRK2 is dysfunctional in the disease state are only now being resolved, but we do know that LRRK2 is, itself, a substrate of multiple kinases and phosphatases and exists in variable phosphorylated states. Autophosphorylation of LRRK2 can impact GTPase and pathological outcomes...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28353276/leucine-rich-repeat-kinase-lrrk2-genetics-and-parkinson-s-disease
#20
Edoardo Monfrini, Alessio Di Fonzo
The discovery of LRRK2 mutations as a cause of Parkinson's disease (PD), including the sporadic late-onset form, established the decisive role of genetics in the field of PD research. Among LRRK2 mutations, the G2019S, mostly lying in a haplotype originating from a common Middle Eastern ancestor, has been identified in different populations worldwide. The G2385R and R1628P variants represent validated risk factors for PD in Asian populations. Here, we describe in detail the origin, the present worldwide epidemiology, and the penetrance of LRRK2 mutations...
2017: Advances in Neurobiology
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