Comparative Genomics of Peroxisome Biogenesis Proteins: Making Sense of the PEX Mess
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
E3 Ubiquitin Ligase SP1 Regulates Peroxisome Biogenesis in Arabidopsis
E3 ubiquitin ligase SP1 regulates peroxisome PNAS PLUS biogenesis in Arabidopsis Ronghui Pana, John Satkovicha, and Jianping Hua,b,1 aDepartment of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824; and bPlant Biology Department, Michigan State University, East Lansing, MI 48824 Edited by Natasha V. Raikhel, Center for Plant Cell Biology, Riverside, CA, and approved September 30, 2016 (received for review August 17, 2016) Peroxisomes are ubiquitous eukaryotic organelles that play pivotal signal type 1) and N-terminal PTS2 sequences, respectively roles in a suite of metabolic processes and often act coordinately (15, 16). In Arabidopsis, PEX5 is also required for PTS2 protein with other organelles, such as chloroplasts and mitochondria. Peroxi- import (16). Two membrane proteins, PEX13 and PEX14, form somes import proteins to the peroxisome matrix by peroxins (PEX the docking site for PEX5 and PEX7 (17, 18). After receptor proteins), but how the function of the PEX proteins is regulated is docking, cargo proteins translocate into the matrix before re- poorly understood. In this study, we identified the Arabidopsis RING ceptors are recycled to the cytosol (19–21). These processes re- (really interesting new gene) type E3 ubiquitin ligase SP1 [suppressor quire the RING (really interesting new gene)-finger peroxins of plastid protein import locus 1 (ppi1) 1] as a peroxisome membrane PEX2,PEX10,andPEX12(22–25), the ATPases PEX1 and protein with a regulatory role in peroxisome protein import. SP1 PEX6 and their membrane tether APEM9 (aberrant peroxisome interacts physically with the two components of the peroxisome morphology 9) and the ubiquitin-conjugating enzyme PEX4 and protein docking complex PEX13–PEX14 and the (RING)-finger per- its membrane anchor PEX22 (26–29). -
2014A Veenhuis Microbial Cell
Microreview www.microbialcell.com De novo peroxisome biogenesis revisited Marten Veenhuis and Ida J. van der Klei* Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, The Netherlands. * Corresponding Author: Ida J. van der Klei, P.O. Box 11103; 9700 CC Groningen, The Netherlands; Tel: +31 50 363 2179/2400; Fax: +31 50 363 2348; E-mail: [email protected] We describe an alternative peroxisome formation made in pex19 cells of both species although the pex19 pathway in yeast pex3 and pex19 cells, which relies on vesicles differed from those present in pex3 cells in that the existence of small peroxisomal remnants that are they contained, besides Pex13, Pex14 and Pex8, also Pex3. present in these cells. This groundbreaking result chal- Pex13 and Pex14 are key components of the matrix protein lenges current models prescribing that peroxisomes receptor docking complex. In the membrane remnants derive de novo from the ER. Our data also has major small amounts of matrix protein were present suggesting implications for the sorting pathway of specific peroxi- that Pex13 and Pex14 were correctly inserted and func- somal membrane proteins (PMPs). We propose a novel tional as receptor docking site. The low matrix content may be explained in that the proteins of the receptor recycling sorting pathway for the PMPs Pex13 and Pex14 that is system (including the RING finger proteins) were not pre- independent of the known Pex3/Pex19 machinery. sent on these structures, thereby preventing recycling of the PTS1 receptor Pex5. Indeed, Pex5 was found associated Peroxisomes are crucial, multifunctional organelles the with the vesicles, whereas other PMPs, e.g. -
Microduplication in the 2P16.1P15 Chromosomal Region Linked To
Lovrecic et al. Molecular Cytogenetics (2018) 11:39 https://doi.org/10.1186/s13039-018-0388-y CASE REPORT Open Access Microduplication in the 2p16.1p15 chromosomal region linked to developmental delay and intellectual disability Luca Lovrecic1* , Chiara Gnan2, Federica Baldan3, Alessandra Franzoni2, Sara Bertok4, Giuseppe Damante5, Bertrand Isidor6 and Borut Peterlin1 Abstract Background: Several patients with the 2p16.1p15 microdeletion syndrome have been reported. However, microduplication in the 2p16.1p15 chromosomal region has only been reported in one case, and milder clinical features were present compared to those attributed to 2p16.1p15 microdeletion syndrome. Some additional cases were deposited in DECIPHER database. Case presentation: In this report we describe four further cases of 2p16.1p15 microduplication in four unrelated probands. They presented with mild gross motor delay, delayed speech and language development, and mild dysmorphic features. In addition, two probands have macrocephaly and one a congenital heart anomaly. Newly described cases share several phenotype characteristics with those detailed in one previously reported microduplication case. Conclusion: The common features among patients are developmental delay, speech delay, mild to moderate intellectual disability and unspecific dysmorphic features. Two patients have bilateral clinodactyly of the 5th finger and two have bilateral 2nd-3rd toes syndactyly. Interestingly, as opposed to the deletion phenotype with some cases of microcephaly, 2 patients are reported -
Supplementary Table 2
Supplementary Table 2. Differentially Expressed Genes following Sham treatment relative to Untreated Controls Fold Change Accession Name Symbol 3 h 12 h NM_013121 CD28 antigen Cd28 12.82 BG665360 FMS-like tyrosine kinase 1 Flt1 9.63 NM_012701 Adrenergic receptor, beta 1 Adrb1 8.24 0.46 U20796 Nuclear receptor subfamily 1, group D, member 2 Nr1d2 7.22 NM_017116 Calpain 2 Capn2 6.41 BE097282 Guanine nucleotide binding protein, alpha 12 Gna12 6.21 NM_053328 Basic helix-loop-helix domain containing, class B2 Bhlhb2 5.79 NM_053831 Guanylate cyclase 2f Gucy2f 5.71 AW251703 Tumor necrosis factor receptor superfamily, member 12a Tnfrsf12a 5.57 NM_021691 Twist homolog 2 (Drosophila) Twist2 5.42 NM_133550 Fc receptor, IgE, low affinity II, alpha polypeptide Fcer2a 4.93 NM_031120 Signal sequence receptor, gamma Ssr3 4.84 NM_053544 Secreted frizzled-related protein 4 Sfrp4 4.73 NM_053910 Pleckstrin homology, Sec7 and coiled/coil domains 1 Pscd1 4.69 BE113233 Suppressor of cytokine signaling 2 Socs2 4.68 NM_053949 Potassium voltage-gated channel, subfamily H (eag- Kcnh2 4.60 related), member 2 NM_017305 Glutamate cysteine ligase, modifier subunit Gclm 4.59 NM_017309 Protein phospatase 3, regulatory subunit B, alpha Ppp3r1 4.54 isoform,type 1 NM_012765 5-hydroxytryptamine (serotonin) receptor 2C Htr2c 4.46 NM_017218 V-erb-b2 erythroblastic leukemia viral oncogene homolog Erbb3 4.42 3 (avian) AW918369 Zinc finger protein 191 Zfp191 4.38 NM_031034 Guanine nucleotide binding protein, alpha 12 Gna12 4.38 NM_017020 Interleukin 6 receptor Il6r 4.37 AJ002942 -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
Zellweger Spectrum Disorder Panel Test Code D4611 Test Summary This panel analyzes 15 genes that have been associated with Zellweger Spectrum Disorders. Turn-Around-Time (TAT)* 3 - 5 weeks Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Commercial Insurance Indications for Testing This panel may be appropriate for individuals with signs and symptoms of a peroxisomal biogenesis disfuction and/or Zellweger syndrome spectrum disorder and/or a family history of these conditions. Test Description This panel analyzes 15 genes that have been associated with Zellweger Spectrum Disorders. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Zellweger syndrome spectrum disorders include Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), an intermediate form and infantile Refsum disease (IRD). Symptoms may include hypotonia, feeding problems, hearing and vision loss, seizures, distinctive facial characteristics and skeletal abnormalities. Zellweger spectrum disorder is estimated to occur in 1/50,000 individuals. Genes ACOX1, AMACR, HSD17B4, PEX1, PEX10, PEX12, PEX13, PEX14, PEX16, PEX19, PEX2, PEX26, PEX3, PEX5, PEX6 Test Methods and Limitations Sequencing is performed on genomic DNA using an Agilent targeted sequence capture method to enrich for the genes on this panel. -
Genetic and Clinical Aspects of Zellweger Spectrum Patients with PEX1 Mutations H Rosewich, a Ohlenbusch, J Ga¨Rtner
1of6 J Med Genet: first published as 10.1136/jmg.2005.033324 on 1 September 2005. Downloaded from ONLINE MUTATION REPORT Genetic and clinical aspects of Zellweger spectrum patients with PEX1 mutations H Rosewich, A Ohlenbusch, J Ga¨rtner ............................................................................................................................... J Med Genet 2005;42:e58 (http://www.jmedgenet.com/cgi/content/full/42/9/e58). doi: 10.1136/jmg.2005.033324 and can survive up to several decades. RCDP is clinically Objective: To analyse the PEX1 gene, the most common and genetically distinctive from the Zellweger syndrome cause for peroxisome biogenesis disorders (PBD), in a spectrum and includes classical RCDP as the prototype and consecutive series of patients with Zellweger spectrum. also milder variants. Patients with classical RCDP have Methods: Mutations were detected by different methods unique clinical symptoms including proximal shortening of including SSCP analyses as a screening technique on the the limbs (rhizomelia), cataracts, and profound psychomotor basis of genomic or cDNA, followed by direct sequencing of retardation. PCR fragments with an abnormal electrophoresis pattern. PBDs can be caused by defects in any of several processes Results: 33 patients were studied. Two common mutations, in organelle formation, including the synthesis of peroxisome c.2528GRA, G843D and c.2098_2098insT, I700YfsX42, membranes, the recognition of newly synthesised peroxiso- accounted for over 80% of all abnormal PEX1 alleles, mal matrix proteins, or any of the downstream steps in emphasising their diagnostic relevance. Most PEX1 mutations peroxisomal protein import. Progress over the last two were distributed over the two AAA cassettes with the two decades has led to the identification of 13 different human functional protein domains, D1 and D2, and the highly PEX genes involved in peroxisome biogenesis, explaining the conserved Walker motifs. -
Lysosomal Exocytosis Releases Pathogenic Α-Synuclein Species
bioRxiv preprint doi: https://doi.org/10.1101/2021.04.10.439302; this version posted April 11, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Lysosomal Exocytosis Releases Pathogenic α-Synuclein Species from Neurons Ying Xue Xie1#, Nima N. Naseri2#, Jasmine Fels1, Parinati Kharel1, Yoonmi Na1, Jacqueline Burré1, Manu Sharma1* 1 Appel Institute for Alzheimer’s Research, and Brain & Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. 2 Department of Chemistry, University of Pennsylvania, Philadelphia, PA, USA. # Equal contribution * Correspondence: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2021.04.10.439302; this version posted April 11, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. SUMMARY Considerable evidence supports the release of pathogenic aggregates of the neuronal protein α-Synuclein (αSyn) into the extracellular space. While this release is proposed to instigate the neuron-to-neuron transmission and spread of αSyn pathology in synucleinopathies including Parkinson’s disease, the molecular-cellular mecha- nism(s) remain unclear. Here we show that pathogenic species of αSyn accumulate within neuronal lysosomes in mouse brains and primary neurons. We then find that neurons release these pathogenic αSyn species via SNARE- dependent lysosomal exocytosis; proposing a central mechanism for exocytosis of aggregated and degradation- resistant proteins from neurons. INTRODUCTION Cytoplasmic aggregates of the synaptic protein αSyn are a characteristic feature of multiple neurodegenerative diseases termed “synucleinopathies”, including Parkinson disease (PD). -
Genome-Wide Insights on Gastrointestinal Nematode
www.nature.com/scientificreports OPEN Genome‑wide insights on gastrointestinal nematode resistance in autochthonous Tunisian sheep A. M. Ahbara1,2, M. Rouatbi3,4, M. Gharbi3,4, M. Rekik1, A. Haile1, B. Rischkowsky1 & J. M. Mwacharo1,5* Gastrointestinal nematode (GIN) infections have negative impacts on animal health, welfare and production. Information from molecular studies can highlight the underlying genetic mechanisms that enhance host resistance to GIN. However, such information often lacks for traditionally managed indigenous livestock. Here, we analysed 600 K single nucleotide polymorphism genotypes of GIN infected and non‑infected traditionally managed autochthonous Tunisian sheep grazing communal natural pastures. Population structure analysis did not fnd genetic diferentiation that is consistent with infection status. However, by contrasting the infected versus non‑infected cohorts using ROH, LR‑GWAS, FST and XP‑EHH, we identifed 35 candidate regions that overlapped between at least two methods. Nineteen regions harboured QTLs for parasite resistance, immune capacity and disease susceptibility and, ten regions harboured QTLs for production (growth) and meat and carcass (fatness and anatomy) traits. The analysis also revealed candidate regions spanning genes enhancing innate immune defence (SLC22A4, SLC22A5, IL‑4, IL‑13), intestinal wound healing/repair (IL‑4, VIL1, CXCR1, CXCR2) and GIN expulsion (IL‑4, IL‑13). Our results suggest that traditionally managed indigenous sheep have evolved multiple strategies that evoke and enhance GIN resistance and developmental stability. They confrm the importance of obtaining information from indigenous sheep to investigate genomic regions of functional signifcance in understanding the architecture of GIN resistance. Small ruminants (sheep and goats) make immense socio-economic and cultural contributions across the globe. -
Inheritest 500 PLUS
Inheritest® 500 PLUS 525 genes Specimen ID: 00000000010 Container ID: H0651 Control ID: Acct #: LCA-BN Phone: SAMPLE REPORT, F-630049 Patient Details Specimen Details Physician Details DOB: 01/01/1991 Date Collected: 08/05/2019 12:00 (Local) Ordering: Age (yyy/mm/dd): 028/07/04 Date Received: 08/06/2019 Referring: Gender: Female Date Entered: 08/06/2019 ID: Patient ID: 00000000010 Date Reported: 08/21/2019 15:29 (Local) NPI: Ethnicity: Unknown Specimen Type: Blood Lab ID: MNEGA Indication: Carrier screening Genetic Counselor: None SUMMARY: POSITIVE POSITIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Spinal muscular atrophy AT RISK AT RISK to be a silent carrier (2+0). For ethnic-specific risk (SMN1) 2 copies of SMN1; positive for revisions see Methods/Limitations. Genetic counseling is NMID: NM_000344 c.*3+80T>G SNP recommended. Risk: AT INCREASED RISK FOR AFFECTED PREGNANCY. See Additional Clinical Information. NEGATIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Cystic fibrosis NEGATIVE This result reduces, but does not eliminate the risk to be a (CFTR) carrier. NMID: NM_000492 Risk: NOT at an increased risk for an affected pregnancy. Fragile X syndrome NEGATIVE: Not a carrier of a fragile X expansion. (FMR1) 29 and 36 repeats NMID: NM_002024 Risk: NOT at an increased risk for an affected pregnancy. ALL OTHER DISORDERS NEGATIVE This result reduces, but does not eliminate the risk to be a carrier. Risk: The individual is NOT at an increased risk for having a pregnancy that is affected with one of the disorders covered by this test. For partner's gene-specific risks, visit www.integratedgenetics.com. -
Downloaded Per Proteome Cohort Via the Web- Site Links of Table 1, Also Providing Information on the Deposited Spectral Datasets
www.nature.com/scientificreports OPEN Assessment of a complete and classifed platelet proteome from genome‑wide transcripts of human platelets and megakaryocytes covering platelet functions Jingnan Huang1,2*, Frauke Swieringa1,2,9, Fiorella A. Solari2,9, Isabella Provenzale1, Luigi Grassi3, Ilaria De Simone1, Constance C. F. M. J. Baaten1,4, Rachel Cavill5, Albert Sickmann2,6,7,9, Mattia Frontini3,8,9 & Johan W. M. Heemskerk1,9* Novel platelet and megakaryocyte transcriptome analysis allows prediction of the full or theoretical proteome of a representative human platelet. Here, we integrated the established platelet proteomes from six cohorts of healthy subjects, encompassing 5.2 k proteins, with two novel genome‑wide transcriptomes (57.8 k mRNAs). For 14.8 k protein‑coding transcripts, we assigned the proteins to 21 UniProt‑based classes, based on their preferential intracellular localization and presumed function. This classifed transcriptome‑proteome profle of platelets revealed: (i) Absence of 37.2 k genome‑ wide transcripts. (ii) High quantitative similarity of platelet and megakaryocyte transcriptomes (R = 0.75) for 14.8 k protein‑coding genes, but not for 3.8 k RNA genes or 1.9 k pseudogenes (R = 0.43–0.54), suggesting redistribution of mRNAs upon platelet shedding from megakaryocytes. (iii) Copy numbers of 3.5 k proteins that were restricted in size by the corresponding transcript levels (iv) Near complete coverage of identifed proteins in the relevant transcriptome (log2fpkm > 0.20) except for plasma‑derived secretory proteins, pointing to adhesion and uptake of such proteins. (v) Underrepresentation in the identifed proteome of nuclear‑related, membrane and signaling proteins, as well proteins with low‑level transcripts. -
Generalised and Conditional Inactivation of Pex Genes in Mice ⁎ Myriam Baes A, , Paul P
CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Biochimica et Biophysica Acta 1763 (2006) 1785–1793 www.elsevier.com/locate/bbamcr Review Generalised and conditional inactivation of Pex genes in mice ⁎ Myriam Baes a, , Paul P. Van Veldhoven b a Laboratory for Cell Metabolism, Campus Gasthuisberg Onderwijs en Navorsing II, bus 823 Herestraat 49 B-3000, Department of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium b Department of Molecular Cell Biology, Division Pharmacology, Katholieke Universiteit Leuven, Leuven, Belgium Received 4 May 2006; received in revised form 17 August 2006; accepted 18 August 2006 Available online 25 August 2006 Abstract During the past 10 years, several Pex genes have been knocked out in the mouse with the purpose to generate models to study the pathogenesis of peroxisome biogenesis disorders and/or to investigate the physiological importance of the Pex proteins. More recently, mice with selective inactivation of a Pex gene in particular cell types were created. The metabolic abnormalities in peroxisome deficient mice paralleled to a large extent those of Zellweger patients. Several but not all of the clinical and histological features reported in patients also occurred in peroxisome deficient mice as for example hypotonia, cortical and cerebellar malformations, endochondral ossification defects, hepatomegaly, liver fibrosis and ultrastructural abnormalities of mitochondria in hepatocytes. Although the molecular origins of the observed pathologies have not yet been resolved, several new insights on the importance of peroxisomes in different tissues have emerged. © 2006 Elsevier B.V. All rights reserved. Keywords: Pex gene; Peroxisome; Knockout; Mouse model; Zellweger syndrome; Conditional gene inactivation 1.