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Leucine rich repeate kinase

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https://www.readbyqxmd.com/read/29760073/regulation-of-myeloid-cell-phagocytosis-by-lrrk2-via-wave2-complex-stabilization-is-altered-in-parkinson-s-disease
#1
Kwang Soo Kim, Paul C Marcogliese, Jungwoo Yang, Steve M Callaghan, Virginia Resende, Elizabeth Abdel-Messih, Connie Marras, Naomi P Visanji, Jana Huang, Michael G Schlossmacher, Laura Trinkle-Mulcahy, Ruth S Slack, Anthony E Lang, David S Park
Leucine-rich repeat kinase 2 ( LRRK2 ) has been implicated in both familial and sporadic Parkinson's disease (PD), yet its pathogenic role remains unclear. A previous screen in Drosophila identified Scar/WAVE (Wiskott-Aldrich syndrome protein-family verproline) proteins as potential genetic interactors of LRRK2 Here, we provide evidence that LRRK2 modulates the phagocytic response of myeloid cells via specific modulation of the actin-cytoskeletal regulator, WAVE2. We demonstrate that macrophages and microglia from LRRK2-G2019S PD patients and mice display a WAVE2-mediated increase in phagocytic response, respectively...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29739947/essential-role-of-linx-islr2-in-the-development-of-the-forebrain-anterior-commissure
#2
Shaniya Abudureyimu, Naoya Asai, Atsushi Enomoto, Liang Weng, Hiroki Kobayashi, Xiaoze Wang, Chen Chen, Shinji Mii, Masahide Takahashi
Linx is a member of the leucine-rich repeat and immunoglobulin family of membrane proteins which has critical roles in the development of the peripheral nervous system and forebrain connectivity. A previous study showed that Linx is expressed in projection neurons in the cortex and in cells that comprise the passage to the prethalamus that form the internal capsule, indicating the involvement of Linx in axon guidance and cell-cell communication. In this study, we found that Linx-deficient mice develop severe hydrocephalus and die perinatally by unknown mechanisms...
May 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29738771/mir-141-3p-is-upregulated-in-esophageal-squamous-cell-carcinoma-and-targets-pleckstrin-homology-domain-leucine-rich-repeat-protein-phosphatase-2-a-negative-regulator-of-the-pi3k-akt-pathway
#3
Osamu Ishibashi, Ichiro Akagi, Yota Ogawa, Takashi Inui
The phosphatidylinositol-3-kinase (PI3K)/AKT pathway is frequently activated in various human cancers and plays essential roles in their development and progression. Accumulating evidence suggests that dysregulated expression of microRNAs (miRNAs) is closely associated with cancer progression and metastasis. Here, we focused on miRNAs that could regulate genes related to the PI3K/AKT pathway in esophageal squamous cell carcinoma (ESCC). To identify upregulated miRNAs and their possible target genes in ESCC, we performed microarray-based integrative analyses of miRNA and mRNA expression levels in three human ESCC cell lines and a normal esophageal epithelial cell line...
May 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29735985/the-serk3-elongated-allele-defines-a-role-for-bir-ectodomains-in-brassinosteroid-signalling
#4
Ulrich Hohmann, Joël Nicolet, Andrea Moretti, Ludwig A Hothorn, Michael Hothorn
The leucine-rich repeat receptor kinase (LRR-RK) BRASSINOSTEROID INSENSITIVE 1 (BRI1) requires a shape-complementary SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK) co-receptor for brassinosteroid sensing and receptor activation 1 . Interface mutations that weaken the interaction between receptor and co-receptor in vitro reduce brassinosteroid signalling responses 2 . The SERK3 elongated (elg) allele3-5 maps to the complex interface and shows enhanced brassinosteroid signalling, but surprisingly no tighter binding to the BRI1 ectodomain in vitro...
May 7, 2018: Nature Plants
https://www.readbyqxmd.com/read/29735704/lrrk2-phosphorylation-of-auxilin-mediates-synaptic-defects-in-dopaminergic-neurons-from-patients-with-parkinson-s-disease
#5
Maria Nguyen, Dimitri Krainc
Recently identified Parkinson's disease (PD) genes involved in synaptic vesicle endocytosis, such as DNAJC6 (auxilin), have further implicated synaptic dysfunction in PD pathogenesis. However, how synaptic dysfunction contributes to the vulnerability of human dopaminergic neurons has not been previously explored. Here, we demonstrate that commonly mutated, PD-linked leucine-rich repeat kinase 2 (LRRK2) mediates the phosphorylation of auxilin in its clathrin-binding domain at Ser627. Kinase activity-dependent LRRK2 phosphorylation of auxilin led to differential clathrin binding, resulting in disrupted synaptic vesicle endocytosis and decreased synaptic vesicle density in LRRK2 patient-derived dopaminergic neurons...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29726283/lactobacillus-plantarum-is-10506-activates-intestinal-stem-cells-in-a-rodent-model
#6
A F Athiyyah, A Darma, R Ranuh, W Riawan, A Endaryanto, F A Rantam, I S Surono, S M Sudarmo
This study investigated the probiotic effect of Lactobacillus plantarum IS-10506 in activating and regenerating leucine-rich repeat-containing G-protein-coupled receptor (Lgr)5- and B lymphoma Moloney murine leukaemia virus insertion region (Bmi)1-expressing intestinal stem cells in rodents following Escherichia coli serotype 055:B5 lipopolysaccharide (LPS) exposure. Male Sprague-Dawley rats (n=64) were randomised into control (KN), LPS (KL), probiotic + LPS (KL-Pr), and sequential probiotic + LPS + probiotic (KPR-7L) groups...
May 4, 2018: Beneficial Microbes
https://www.readbyqxmd.com/read/29723186/active-photosynthetic-inhibition-mediated-by-mpk3-mpk6-is-critical-to-effector-triggered-immunity
#7
Jianbin Su, Liuyi Yang, Qiankun Zhu, Hongjiao Wu, Yi He, Yidong Liu, Juan Xu, Dean Jiang, Shuqun Zhang
Extensive research revealed tremendous details about how plants sense pathogen effectors during effector-triggered immunity (ETI). However, less is known about downstream signaling events. In this report, we demonstrate that prolonged activation of MPK3 and MPK6, two Arabidopsis pathogen-responsive mitogen-activated protein kinases (MPKs), is essential to ETI mediated by both coiled coil-nucleotide binding site-leucine rich repeats (CNLs) and toll/interleukin-1 receptor nucleotide binding site-leucine rich repeats (TNLs) types of R proteins...
May 3, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29719501/acetylome-in-human-fibroblasts-from-parkinson-s-disease-patients
#8
Sokhna M S Yakhine-Diop, Mario Rodríguez-Arribas, Guadalupe Martínez-Chacón, Elisabet Uribe-Carretero, Rubén Gómez-Sánchez, Ana Aiastui, Adolfo López de Munain, José M Bravo-San Pedro, Mireia Niso-Santano, Rosa A González-Polo, José M Fuentes
Parkinson's disease (PD) is a multifactorial neurodegenerative disorder. The pathogenesis of this disease is associated with gene and environmental factors. Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent genetic cause of familial and sporadic PD. Moreover, posttranslational modifications, including protein acetylation, are involved in the molecular mechanism of PD. Acetylation of lysine proteins is a dynamic process that is modulated in PD. In this descriptive study, we characterized the acetylated proteins and peptides in primary fibroblasts from idiopathic PD (IPD) and genetic PD harboring G2019S or R1441G LRRK2 mutations...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29717018/medicago-plants-control-nodulation-by-regulating-proteolysis-of-the-receptor-like-kinase-dmi2
#9
Huairong Pan, Dong Wang
Plants use receptor-like kinases to monitor environmental changes and transduce signals into plant cells. The Medicago truncatula DOES NOT MAKE INFECTIONS 2 (DMI2) protein functions as a co-receptor of rhizobial signals to initiate nodule development and rhizobial infection during nitrogen-fixing symbiosis, but the mechanisms regulating DMI2 protein level and folding are still unknown. Here we report that DMI2 protein abundance changes during nitrogen-fixing symbiosis. DMI2 accumulates in the nodules and is induced by rhizobia treatment through a posttranscriptional process...
May 1, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29705795/leucine-rich-repeat-kinase-2-in-parkinson-s-disease-updated-from-pathogenesis-to-potential-therapeutic-target
#10
Jinhua Chen, Ying Chen, Jiali Pu
BACKGROUND: Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain. The pathogenesis of PD is not fully understood but is likely caused by a combination of genetic and environmental factors. Several genes are associated with the onset and progression of familial PD. There is increasing evidence that leucine-rich repeat kinase 2 (LRRK2) plays a significant role in PD pathophysiology. SUMMARY: Many studies have been conducted to elucidate the functions of LRRK2 and identify effective LRRK2 inhibitors for PD treatment...
April 27, 2018: European Neurology
https://www.readbyqxmd.com/read/29704272/targeted-therapies-for-parkinson-s-disease-from-genetics-to-the-clinic
#11
REVIEW
S Pablo Sardi, Jesse M Cedarbaum, Patrik Brundin
The greatest unmet medical need in Parkinson's disease (PD) is treatments that slow the relentless progression of symptoms. The discovery of genetic variants causing and/or increasing the risk for PD has provided the field with a new arsenal of potential therapies ready to be tested in clinical trials. We highlight 3 of the genetic discoveries (α-synuclein, glucocerebrosidase, and leucine-rich repeat kinase) that have prompted new therapeutic approaches now entering the clinical stages. We are at an exciting juncture in the journey to developing disease-modifying treatments based on knowledge of PD genetics and pathology...
April 27, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29700116/comparative-analysis-of-parkinson-s-disease-associated-genes-reveals-altered-survival-and-bioenergetics-of-parkin-deficient-dopamine-neurons-in-mice
#12
Nicolas Giguere, Consiglia Pacelli, Caroline Saumure, Marie-Josee Bourque, Diana Matheoud, Daniel Levesque, Ruth S Slack, David S Park, Louis-Eric Trudeau
Many mutations in genes encoding proteins such as parkin, PTEN-induced putative kinase 1 (PINK1), protein deglycase DJ-1 (DJ-1 or PARK7), leucine-rich repeat kinase 2 (LRRK2), and α-synuclein have been linked to familial forms of Parkinson's disease (PD). The consequences of these mutations, such as altered mitochondrial function and pathological protein aggregation, are starting to be better understood. However, little is known about the mechanisms explaining why alterations in such diverse cellular mechanisms lead to the selective loss of dopamine (DA) neurons in the substantia nigra (SNc) in the brain of individuals with PD...
April 26, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29693156/downregulation-of-lgr6-inhibits-proliferation-and-invasion-and-increases-apoptosis-in-human-colorectal-cancer
#13
Fei Wang, Chun-Qian Dai, Li-Rong Zhang, Cao Bing, Jun Qin, Yi-Fei Liu
The aim of the present study was to analyze the role of leucine‑rich repeat‑containing G‑protein coupled receptor 6 (Lgr6) in the proliferation and invasion of colorectal cancer (CRC) cells, and to investigate its possible mechanisms. The expression of Lgr6 in CRC tissues was observed by real time‑quantitative polymerase chain reaction and western blotting. Then cell viability, apoptosis and cell invasion was measured by MTT, flow cytometry or Matrigel‑Transwell system, respectively in CRC cells after transfected with Lgr6 siRNA or Lgr6 vector...
April 18, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29680709/parkinson-s-disease-like-burst-firing-activity-in-subthalamic-nucleus-induced-by-aav-%C3%AE-synuclein-is-normalized-by-lrrk2-modulation
#14
Michael Aagaard Andersen, Kenneth Vielsted Christensen, Lassina Badolo, Garrick Paul Smith, Ross Jeggo, Poul Henning Jensen, Kathrine Just Andersen, Florence Sotty
Parkinson's disease (PD) affects motor function through degenerative processes and synaptic transmission impairments in the basal ganglia. None of the treatments available delays or stops the progression of the disease. While α-synuclein pathological accumulation represents a hallmark of the disease in its idiopathic form, leucine rich repeat kinase 2 (LRRK2) is genetically associated with familial and sporadic forms of PD. The genetic information suggests that LRRK2 kinase activity plays a role in the pathogenesis of the disease...
April 19, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29678858/the-receptor-like-kinase-atvrlk1-regulates-secondary-cell-wall-thickening
#15
Cheng Huang, Rui Zhang, Jinshan Gui, Yu Zhong, Laigeng Li
During the growth and development of land plants, some specialized cells, such as tracheary elements, undergo secondary cell wall thickening. Secondary cell walls contain additional lignin, compared with primary cell walls, thus providing mechanical strength and potentially improving defenses against pathogens. However, the molecular mechanisms that initiate wall thickening are unknown. In this study, we identified an Arabidopsis thaliana leucine-rich repeat receptor-like kinase, encoded by AtVRLK1 (Vascular-Related RLK 1), that is specifically expressed in cells undergoing secondary cell wall thickening...
April 20, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29671916/assembly-and-annotation-of-a-draft-genome-sequence-for-glycine-latifolia-a-perennial-wild-relative-of-soybean
#16
Qiong Liu, Sungyul Chang, Glen L Hartman, Leslie L Domier
Glycine latifolia (Benth.) Newell & Hymowitz (2n=40), one of the 27 wild perennial relatives of soybean, possesses genetic diversity and agronomically favorable traits that are lacking in soybean. Here, we report the 939-Mb draft genome assembly of G. latifolia (PI 559298) using exclusively linked-reads sequenced from a single Chromium library. We organized scaffolds into 20 chromosome-scale pseudomolecules utilizing two genetic maps and the Glycine max (L.) Merr. genome sequence. High copy numbers of putative 91-bp centromere-specific tandem repeats were observed in consecutive blocks within predicted pericentromeric regions on several pseudomolecules...
April 19, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29665080/clustering-of-motor-and-nonmotor-traits-in-leucine-rich-repeat-kinase-2-g2019s-parkinson-s-disease-nonparkinsonian-relatives-a-multicenter-family-study
#17
Tiago A Mestre, Claustre Pont-Sunyer, Farah Kausar, Naomi P Visanji, Taneera Ghate, Barbara S Connolly, Carmen Gasca-Salas, Drew S Kern, Jennifer Jain, Elizabeth J Slow, Achinoam Faust-Socher, Meike Kasten, Pettarusp M Wadia, Cindy Zadikoff, Prakash Kumar, Ronald M de Bie, Teri Thomsen, Anthony E Lang, Birgitt Schüle, Christine Klein, Eduardo Tolosa, Connie Marras
OBJECTIVES: The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first-degree relatives of PD leucine-rich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features. METHODS: We included nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases and unrelated healthy controls participating in established multiplex family LRRK2 cohorts...
April 17, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29663867/coiled-coil-and-leucine-rich-repeat-domain-of-the-potyvirus-resistance-protein-pvr4-has-distinct-role-in-signaling-and-pathogen-recognition
#18
Saet-Byul Kim, Hye-Young Lee, Eun-Hye Choi, Eunsook Park, Jihyun Kim, Ki-Beom Moon, Hyun-Soon Kim, Doil Choi
The pepper Pvr4 encoding coiled-coil (CC) nucleotide-binding (NB) leucine-rich repeat (LRR) protein (CC-NLR) confer hypersensitive resistance (HR) to potyviruses, including Pepper mottle virus (PepMoV) by recognizing the viral avirulence protein, NIb. To figure out the Pvr4-mediated HR mechanism, we analyzed the signaling component genes and structure-function relationships of Pvr4 using chimeras and deletion mutants in Nicotiana benthamiana. Molecular chaperone components including HSP90, SGT1 and RAR1 were required, while plant hormones and mitogen-activated protein (MAP) kinase signaling components had little effect on Pvr4-NIb-mediated HR cell death...
April 17, 2018: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29659493/cloning-characterization-and-functional-investigation-of-vahaesa-from-vitis-amurensis-inoculated-with-plasmopara-viticola
#19
Shaoli Liu, Chi Zhang, Nan Chao, Jiang Lu, Yali Zhang
Plant pattern recognition receptors (PRRs) are essential for immune responses and establishing symbiosis. Plants detect invaders via the recognition of pathogen-associated molecular patterns (PAMPs) by PRRs. This phenomenon is termed PAMP-triggered immunity (PTI). We investigated disease resistance in Vitis amurensis to identify PRRs that are important for resistance against downy mildew, analyzed the PRRs that were upregulated by incompatible Plasmopara viticola infection, and cloned the full-length cDNA of the VaHAESA gene...
April 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29628444/ph-domain-leucine-rich-repeat-protein-phosphatase-2-phlpp2-regulates-g-protein-coupled-receptor-kinase-5-grk5-induced-cardiac-hypertrophy-in-vitro
#20
Szu-Tsen Yeh, Cristina M Zambrano, Walter J Koch, Nicole H Purcell
PH domain leucine-rich repeat protein phosphatase (PHLPP) is a serine/threonine phosphatase that has been shown to regulate cell growth and survival through dephosphorylation of several members of the AGC family of kinases. G-protein coupled receptor kinase 5 (GRK5) is an AGC kinase that regulates phenylephrine (PE) induced cardiac hypertrophy through its non-canonical function of directly targeting proteins to the nucleus to regulate transcription. Here we investigated the possibility that the PHLPP2 isoform can regulate GRK5 induced cardiomyocyte hypertrophy in neonatal rat ventricular myocytes (NRVMs)...
April 8, 2018: Journal of Biological Chemistry
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