scholarly journals RUFY4 exists as two translationally regulated isoforms, that localize to the mitochondrion in activated macrophages

2021 ◽  
Vol 8 (7) ◽  
pp. 202333
Author(s):  
Jan Valečka ◽  
Voahirana Camosseto ◽  
David G. McEwan ◽  
Seigo Terawaki ◽  
Zhuangzhuang Liu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Translation Initiation ◽  
Messenger Rna ◽  
Activated Macrophages ◽  
Truncated Form ◽  
Fyve Domain ◽  
Alternative Translation ◽  
Translation Initiation Codon ◽  
Molecular Patterns

We report here that RUFY4, a newly characterized member of the ‘RUN and FYVE domain-containing’ family of proteins previously associated with autophagy enhancement, is highly expressed in alveolar macrophages (AM). We show that RUFY4 interacts with mitochondria upon stimulation by microbial-associated molecular patterns of AM and dendritic cells. RUFY4 interaction with mitochondria and other organelles is dependent on a previously uncharacterized OmpH domain located immediately upstream of its C-terminal FYVE domain. Further, we demonstrate that rufy4 messenger RNA can be translated from an alternative translation initiation codon, giving rise to a N-terminally truncated form of the molecule lacking most of its RUN domain and with enhanced potential for its interaction with mitochondria. Our observations point towards a role of RUFY4 in selective mitochondria clearance in activated phagocytes.

scholarly journals The Role of eIF1 in Translation Initiation Codon Selection in Caenorhabditiselegans

Genetics ◽  
2010 ◽  
Vol 186 (4) ◽  
pp. 1187-1196 ◽  
Author(s):  
Lisa L. Maduzia ◽  
Anais Moreau ◽  
Nausicaa Poullet ◽  
Sebastien Chaffre ◽  
Yinhua Zhang
Keyword(s):  
Translation Initiation ◽  
Initiation Codon ◽  
Translation Initiation Codon ◽  
Codon Selection

scholarly journals Pathogen-Associated Molecular Patterns Induced Crosstalk between Dendritic Cells, T Helper Cells, and Natural Killer Helper Cells Can Improve Dendritic Cell Vaccination

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Tammy Oth ◽  
Joris Vanderlocht ◽  
Catharina H. M. J. Van Elssen ◽  
Gerard M. J. Bos ◽  
Wilfred T. V. Germeraad
Keyword(s):  
Dendritic Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Specific Pattern ◽  
Dendritic Cell Vaccination ◽  
T Helper ◽  
Cell Responses ◽  
Helper Cells ◽  
Molecular Patterns

A coordinated cellular interplay is of crucial importance in both host defense against pathogens and malignantly transformed cells. The various interactions of Dendritic Cells (DC), Natural Killer (NK) cells, and T helper (Th) cells can be influenced by a variety of pathogen-associated molecular patterns (PAMPs) and will lead to enhanced CD8+effector T cell responses. Specific Pattern Recognition Receptor (PRR) triggering during maturation enables DC to enhance Th1 as well as NK helper cell responses. This effect is correlated with the amount of IL-12p70 released by DC. Activated NK cells are able to amplify the proinflammatory cytokine profile of DC via the release of IFN-γ. The knowledge on how PAMP recognition can modulate the DC is of importance for the design and definition of appropriate therapeutic cancer vaccines. In this review we will discuss the potential role of specific PAMP-matured DC in optimizing therapeutic DC-based vaccines, as some of these DC are efficiently activating Th1, NK cells, and cytotoxic T cells. Moreover, to optimize these vaccines, also the inhibitory effects of tumor-derived suppressive factors, for example, on the NK-DC crosstalk, should be taken into account. Finally, the suppressive role of the tumor microenvironment in vaccination efficacy and some proposals to overcome this by using combination therapies will be described.

scholarly journals AUGmenting the proteome: Novel initiation codons and their role in protein isoform generation

2015 ◽  
Vol 37 (2) ◽  
pp. 19-23
Author(s):  
Mark J. Coldwell ◽  
Joanne L. Cowan
Keyword(s):  
Alternative Splicing ◽  
Translation Initiation ◽  
Messenger Rna ◽  
Genetic Material ◽  
Protein Sequencing ◽  
Protein Isoforms ◽  
Alternative Promoters ◽  
Alternative Translation ◽  
Initial Hypothesis ◽  
Protein Isoform

As the field of molecular biology developed, and the understanding of how inherited genetic material results in the expression of proteins was established, the initial hypothesis was that one gene gave rise to one protein1. As researchers delved deeper into the organization of the genetic code and advances in messenger RNA (mRNA) and protein sequencing were subsequently made, it has become abundantly clear that multiple mechanisms exist meaning that many mRNAs encode more than one version of a protein. Although alternative promoters and alternative splicing play a considerable role in the generation of protein isoforms, in this article we discuss how usage of alternative translation initiation codons in eukaryotes can also lead to an expanded proteome.

Impaired Platelet Function in a P2Y12-Deficient Patient Caused by a Mutation in the Translation Initiation Codon.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 742-742
Author(s):  
Masamichi Shiraga ◽  
Shigeki Miyata ◽  
Tsuyoshi Kamae ◽  
Hisashi Kato ◽  
Teruo Kiyoi ◽  
...  
Keyword(s):  
Platelet Function ◽  
Translation Initiation ◽  
Initiation Codon ◽  
High Shear ◽  
Integrin Αiibβ3 ◽  
Dependent Signal ◽  
Translation Initiation Codon ◽  
High Concentrations ◽  
Platelet Spreading

Abstract Recent studies have demonstrated that ADP plays a critical role in platelet activation. Platelets possess at least two major G protein-coupled ADP receptors that are largely responsible for platelet responses to ADP: P2Y1 and P2Y12. P2Y12 is the therapeutic target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel, and its congenital deficiency results in a bleeding disorder. In this study, we have identified a patient with the congenital P2Y12 deficiency and analyzed the role of P2Y12 in platelet function. The proband (OSP-1) is a 67-year-old Japanese female with a lifelong history of easy bruising. In response to high concentrations of agonists OSP-1’s platelets showed a specifically impaired aggregation to ADP stimulation. The impaired platelet aggregation was neither improved even at 100 μM ADP stimulation nor reduced by adding 1 μM AR-C69931MX, a specific P2Y12 antagonist. ADP induced platelet shape change normally and failed to inhibit PGE1-stimulated cAMP accumulation in OSP-1 platelets, further suggesting the defect in P2Y12 dependent signal. Molecular genetic analysis revealed that OSP-1 was a homozygous for a mutation in the translation initiation codon (ATG to AGG) in the P2Y12 gene. HEK293 cells transfected with wild-type P2Y12 construct expressed a 60 kD-protein, while cells transfected with mutant P2Y12 construct failed to express any related protein. These data confirmed that the mutation was responsible for the deficiency in P2Y12 and denied the possibility that the substitution might induce an alternative translation starting at downstream ATGs leading to an expression of shorter form of P2Y12. Platelet spreading onto immobilized fibrinogen was impaired in OSP-1 platelets as well as in control platelets in the presence of 1 μM AR-C69931MX. Under static conditions, activation of integrin αIIbβ3 measured by PAC1-binding in OSP-1 platelets was only 5 to 12 % of controls even at high concentrations of PAR1-TRAP, PAR4-TRAP or U46619. These results suggest that ADP released by Gq-coupled receptors and P2Y12-dependent signal are critical for sustained activation of integrin αIIbβ3. Real time observations of thrombogenesis on a type I collagen-coated surface under a high shear rate (2000 s−1) revealed that thrombi were unstable. Most of the aggregates of OSP-1 platelets were unable to resist against high shear stress and loosely-attached aggregates came off into the blood stream. Thrombus height and volume measured at the plateau phase was 50% of control. Our data suggest that secretion of endogenous ADP and subsequent P2Y12-mediated signals are critical for platelet spreading, stable integrin αIIbβ3 activation and, as a consequence, for stabilization of thrombus. These results provide a novel insight for the role of P2Y12 and endogenous ADP released into a limited space between thrombus-forming platelets.

scholarly journals The Role of Lipopeptidophosphoglycan in the Immune Response toEntamoeba histolytica

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Isabel Wong-Baeza ◽  
Marcela Alcántara-Hernández ◽  
Ismael Mancilla-Herrera ◽  
Itzmel Ramírez-Saldívar ◽  
Lourdes Arriaga-Pizano ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Amebic Liver Abscess ◽  
Disease Development ◽  
Dependent Manner ◽  
Surface Molecule ◽  
Adaptive Immune ◽  
Molecular Patterns

The sensing of Pathogen Associated Molecular Patterns (PAMPs) by innate immune receptors, such as Toll-like receptors (TLRs), is the first step in the inflammatory response to pathogens.Entamoeba histolytica, the etiological agent of amebiasis, has a surface molecule with the characteristics of a PAMP. This molecule, which was termed lipopeptidophosphoglycan (LPPG), is recognized through TLR2 and TLR4 and leads to the release of cytokines from human monocytes, macrophages, and dendritic cells; LPPG-activated dendritic cells have increased expression of costimulatory molecules. LPPG activates NKT cells in a CD1d-dependent manner, and this interaction limits amebic liver abscess development. LPPG also induces antibody production, and anti-LPPG antibodies prevent disease development in animal models of amebiasis. Because LPPG is recognized by both the innate and the adaptive immune system (it is a “Pamptigen”), it may be a good candidate to develop a vaccine againstE. histolyticainfection and an effective adjuvant.

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