scholarly journals TRAPPopathies: An emerging set of disorders linked to variations in the genes encoding transport protein particle (TRAPP)‐associated proteins

Traffic ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 5-26 ◽  
Author(s):  
Michael Sacher ◽  
Nassim Shahrzad ◽  
Hiba Kamel ◽  
Miroslav P. Milev
Keyword(s):  
Transport Protein ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Protein Particle

scholarly journals Pathogenic Determinants of the Mycobacterium kansasii Complex: An Unsuspected Role for Distributive Conjugal Transfer

2021 ◽  
Vol 9 (2) ◽  
pp. 348
Author(s):  
Florian Tagini ◽  
Trestan Pillonel ◽  
Claire Bertelli ◽  
Katia Jaton ◽  
Gilbert Greub
Keyword(s):  
Genomic Analysis ◽  
Comparative Genomic ◽  
Mycobacterium Kansasii ◽  
Type Vii Secretion ◽  
A Genome ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Immunosuppressed Patients ◽  
Type Vii Secretion System ◽  
Clinical Records

The Mycobacterium kansasii species comprises six subtypes that were recently classified into six closely related species; Mycobacterium kansasii (formerly M. kansasii subtype 1), Mycobacterium persicum (subtype 2), Mycobacterium pseudokansasii (subtype 3), Mycobacterium ostraviense (subtype 4), Mycobacterium innocens (subtype 5) and Mycobacterium attenuatum (subtype 6). Together with Mycobacterium gastri, they form the M. kansasii complex. M. kansasii is the most frequent and most pathogenic species of the complex. M. persicum is classically associated with diseases in immunosuppressed patients, and the other species are mostly colonizers, and are only very rarely reported in ill patients. Comparative genomics was used to assess the genetic determinants leading to the pathogenicity of members of the M. kansasii complex. The genomes of 51 isolates collected from patients with and without disease were sequenced and compared with 24 publicly available genomes. The pathogenicity of each isolate was determined based on the clinical records or public metadata. A comparative genomic analysis showed that all M. persicum, M. ostraviense, M innocens and M. gastri isolates lacked the ESX-1-associated EspACD locus that is thought to play a crucial role in the pathogenicity of M. tuberculosis and other non-tuberculous mycobacteria. Furthermore, M. kansasii was the only species exhibiting a 25-Kb-large genomic island encoding for 17 type-VII secretion system-associated proteins. Finally, a genome-wide association analysis revealed that two consecutive genes encoding a hemerythrin-like protein and a nitroreductase-like protein were significantly associated with pathogenicity. These two genes may be involved in the resistance to reactive oxygen and nitrogen species, a required mechanism for the intracellular survival of bacteria. Three non-pathogenic M. kansasii lacked these genes likely due to two distinct distributive conjugal transfers (DCTs) between M. attenuatum and M. kansasii, and one DCT between M. persicum and M. kansasii. To our knowledge, this is the first study linking DCT to reduced pathogenicity.

scholarly journals A novel putative microtubule-associated protein is involved in arbuscule development during arbuscular mycorrhiza formation

2021 ◽  
Author(s):  
Tania Ho-Plágaro ◽  
Raúl Huertas ◽  
María I Tamayo-Navarrete ◽  
Elison Blancaflor ◽  
Nuria Gavara ◽  
...  
Keyword(s):  
Plant Root ◽  
Arbuscular Mycorrhizal ◽  
Host Cells ◽  
Root Cells ◽  
Filament Dynamics ◽  
Fungal Structure ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Mycorrhizal Development

Abstract The formation of arbuscular mycorrhizal (AM) symbiosis requires plant root host cells to undergo major structural and functional reprogramming in order to house the highly branched AM fungal structure for the reciprocal exchange of nutrients. These morphological modifications are associated with cytoskeleton remodelling. However, molecular bases and the role of microtubules (MTs) and actin filament dynamics during AM formation are largely unknown. In this study, the tomato tsb gene, belonging to a Solanaceae group of genes encoding MT-associated proteins for pollen development, was found to be highly expressed in root cells containing arbuscules. At earlier stages of mycorrhizal development, tsb overexpression enhanced the formation of highly developed and transcriptionally active arbuscules, while tsb silencing hampers the formation of mature arbuscules and represses arbuscule functionality. However, at later stages of mycorrhizal colonization, tsb OE roots accumulate fully developed transcriptionally inactive arbuscules, suggesting that the collapse and turnover of arbuscules might be impaired by TSB accumulation. Imaging analysis of the MT cytoskeleton in cortex root cells overexpressing tsb revealed that TSB is involved in MT-bundling. Taken together, our results provide unprecedented insights into the role of novel MT-associated protein in MT rearrangements throughout the different stages of the arbuscule life cycle.

scholarly journals Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F.

1992 ◽  
Vol 12 (12) ◽  
pp. 5620-5631 ◽  
Author(s):  
B Shan ◽  
X Zhu ◽  
P L Chen ◽  
T Durfee ◽  
Y Yang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Mammalian Cells ◽  
Leucine Zipper ◽  
T Antigen ◽  
Transactivation Domain ◽  
Recognition Sequence ◽  
Cellular Genes ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Transcription Factor E2f

The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F.

Hypertrophic cardiomyopathy: genetics

ESC CardioMed ◽  
2018 ◽  
pp. 1443-1450
Author(s):  
Mohammed Majid Akhtar ◽  
Luis Rocha Lopes
Keyword(s):  
Genetic Testing ◽  
Hypertrophic Cardiomyopathy ◽  
Mapk Pathway ◽  
Glycogen Storage ◽  
Cellular Level ◽  
Causative Mutation ◽  
Clinical Role ◽  
Genes Encoding ◽  
Associated Proteins

Hypertrophic cardiomyopathy is most commonly transmitted as an autosomal dominant trait, caused by mutations in genes encoding cardiac sarcomere and associated proteins. Knowledge of the genetic pathophysiology of the disease has advanced significantly since the initial identification of a point mutation in the beta-myosin heavy chain (MYH7) gene in 1990. Other genetic causes of the disease include mutations in genes coding for proteins implicated in calcium handling or which form part of the cytoskeleton. The recent emergence of next-generation sequencing allows quicker and less expensive identification of causative mutations. However, a causative mutation is not identified in up to 50% of probands. At present, the primary clinical role of genetic testing in hypertrophic cardiomyopathy is in the context of familial screening, allowing the identification of those at risk of developing the condition. Genetic testing can also be used to exclude genocopies, particularly in the presence of certain diagnostic ‘red flag’ features, where lysosomal, glycogen storage, neuromuscular or Ras-MAPK pathway disorders may be suspected. The role of individual mutations in predicting prognosis is limited at present. However, the higher incidence of sudden cardiac death in the presence of a family history of such, suggests that genetics play a significant role in determining outcome. With an increased understanding of the impact of these mutations on a cellular level and on longer-term clinical outcomes, the aim in future for gene and mutation specific prognosis or potential disease-modifying therapy is closer.

scholarly journals Interactions between Transport Protein Particle (TRAPP) complexes and RabGTPases in Arabidopsis

2019 ◽  
Vol 100 (2) ◽  
pp. 279-297 ◽  
Author(s):  
Monika Kalde ◽  
Liam Elliott ◽  
Raksha Ravikumar ◽  
Katarzyna Rybak ◽  
Melina Altmann ◽  
...  
Keyword(s):  
Transport Protein ◽  
Protein Particle

scholarly journals Distribution and Genetic Diversity of the ABC Transporter Lipoproteins PiuA and PiaA within Streptococcus pneumoniae and Related Streptococci

2006 ◽  
Vol 188 (3) ◽  
pp. 1031-1038 ◽  
Author(s):  
Rachael H. Whalan ◽  
Simon G. P. Funnell ◽  
Lucas D. Bowler ◽  
Michael J. Hudson ◽  
Andrew Robinson ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Streptococcus Pneumoniae ◽  
Oral Streptococci ◽  
Pneumococcal Infections ◽  
Closely Related Species ◽  
Streptococcus Oralis ◽  
Amino Acid Divergence ◽  
Genes Encoding ◽  
Associated Proteins ◽  
Nucleotide Divergence

ABSTRACT Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. The existence of approximately 90 antigenically distinct capsular serotypes has greatly complicated the development of an effective pneumococcal vaccine. Virulence-associated proteins common and conserved among all capsular types now represent the best strategy to combat pneumococcal infections. PiuA and PiaA are the lipoprotein components of two pneumococcal iron ABC transporters and are required for full virulence in mouse models of infection. Here we describe a study of the distribution and genetic diversity of PiuA and PiaA within typical and atypical S. pneumoniae, Streptococcus oralis, and Streptococcus mitis strains. The genes encoding both PiuA and PiaA were present in all typical pneumococci tested, (covering 20 and 27 serotypes, respectively). The piuA gene was highly conserved within the typical pneumococci (0.3% nucleotide divergence), but was also present in “atypical” pneumococci and the closely related species S. mitis and S. oralis, showing up to 10.4% nucleotide divergence and 7.5% amino acid divergence from the typical pneumococcal alleles. Conversely, the piaA gene was found to be specific to typical pneumococci, 100% conserved, and absent from the oral streptococci, including isolates of S. mitis known to possess pneumolysin and autolysin. These are desirable qualities for a vaccine candidate and as a diagnostic tool for S. pneumoniae.

Identification of Francisella tularensis genes encoding exported membrane-associated proteins using TnphoA mutagenesis of a genomic library

2004 ◽  
Vol 37 (4) ◽  
pp. 205-213 ◽  
Author(s):  
Robert D. Gilmore ◽  
Rendi Murphree Bacon ◽  
Steven L. Sviat ◽  
Jeannine M. Petersen ◽  
Scott W. Bearden
Keyword(s):  
Francisella Tularensis ◽  
Genomic Library ◽  
Genes Encoding ◽  
Associated Proteins

Biochemical consequences of sedlin mutations that cause spondyloepiphyseal dysplasia tarda

2009 ◽  
Vol 423 (2) ◽  
pp. 233-242 ◽  
Author(s):  
Mei Y. Choi ◽  
Caleb C. Y. Chan ◽  
Danny Chan ◽  
Keith D. K. Luk ◽  
Kathryn S. E. Cheah ◽  
...  
Keyword(s):  
Late Onset ◽  
Transport Protein ◽  
Missense Mutations ◽  
Wild Type ◽  
Spondyloepiphyseal Dysplasia ◽  
Type Protein ◽  
Wild Type Protein ◽  
Protein Particle ◽  
Spondyloepiphyseal Dysplasia Tarda

SEDT (spondyloepiphyseal dysplasia tarda) is a late-onset X-linked recessive skeletal dysplasia caused by mutations in the gene SEDL coding for sedlin. In the present paper, we investigated four missense mutations observed in SEDT and compare biochemical and cellular characteristics relative to the wild-type protein to address the mechanism of disease and to gain insight into the function of the sedlin protein. In situ hybridization and immunohistochemical experiments in mouse growth plates revealed sedlin to be predominantly expressed in proliferating and hypertrophic chondrocytes. Cell culture studies showed that the wild-type protein localized predominantly in the vicinity of the nucleus and the Golgi, with further localization around the cytoplasm, whereas mutation resulted in mislocalization. The D47Y mutant was expressed similarly to the wild-type, but the S73L, F83S and V130D mutants showed particularly low levels of expression that were rescued in the presence of the proteasome inhibitor MG132 (benzyloxycarbonyl-leucylleucylleucinal). Furthermore, whereas the D47Y mutant folded similarly and had similar stability to the wild-type sedlin as shown by CD and fluorescence, the S73L, F83S and V130D mutants all misfolded during expression. Two independent assays showed that the D47Y mutation resulted in an increased affinity for the transport protein particle component Bet3 compared with the wild-type sedlin. Our results suggest that the sedlin mutations S73L, F83S and V130D cause SEDT by sedlin misfolding, whereas the D47Y mutation may influence normal TRAPP (transport protein particle) dynamics.

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