scholarly journals eIF4E and Interactors from Unicellular Eukaryotes

2020 ◽  
Vol 21 (6) ◽  
pp. 2170
Author(s):  
Daniela Ross-Kaschitza ◽  
Michael Altmann
Keyword(s):  
Leishmania Major ◽  
Yeast Species ◽  
Life Cycle Stage ◽  
Initiation Factor ◽  
Marine Microorganisms ◽  
Protozoan Parasites ◽  
Interacting Protein ◽  
Unicellular Eukaryotes ◽  
Unicellular Organisms ◽  
And Function

eIF4E, the mRNA cap-binding protein, is well known as a general initiation factor allowing for mRNA-ribosome interaction and cap-dependent translation in eukaryotic cells. In this review we focus on eIF4E and its interactors in unicellular organisms such as yeasts and protozoan eukaryotes. In a first part, we describe eIF4Es from yeast species such as Saccharomyces cerevisiae, Candida albicans, and Schizosaccharomyces pombe. In the second part, we will address eIF4E and interactors from parasite unicellular species—trypanosomatids and marine microorganisms—dinoflagellates. We propose that different strategies have evolved during evolution to accommodate cap-dependent translation to differing requirements. These evolutive “adjustments” involve various forms of eIF4E that are not encountered in all microorganismic species. In yeasts, eIF4E interactors, particularly p20 and Eap1 are found exclusively in Saccharomycotina species such as S. cerevisiae and C. albicans. For protozoan parasites of the Trypanosomatidae family beside a unique cap4-structure located at the 5′UTR of all mRNAs, different eIF4Es and eIF4Gs are active depending on the life cycle stage of the parasite. Additionally, an eIF4E-interacting protein has been identified in Leishmania major which is important for switching from promastigote to amastigote stages. For dinoflagellates, little is known about the structure and function of the multiple and diverse eIF4Es that have been identified thanks to widespread sequencing in recent years.

Cell-to-Cell Heterogeneity in Trypanosomes

2021 ◽  
Vol 75 (1) ◽  
Author(s):  
Vanessa Luzak ◽  
Lara López-Escobar ◽  
T. Nicolai Siegel ◽  
Luisa M. Figueiredo
Keyword(s):  
Single Molecule ◽  
Life Cycle Stage ◽  
Surface Glycoprotein ◽  
Annual Review ◽  
Publication Date ◽  
Cell Heterogeneity ◽  
Protozoan Parasites ◽  
Recent Developments ◽  
Unicellular Organisms ◽  
Hostile Environments

Recent developments in single-cell and single-molecule techniques have revealed surprising levels of heterogeneity among isogenic cells. These advances have transformed the study of cell-to-cell heterogeneity into a major area of biomedical research, revealing that it can confer essential advantages, such as priming populations of unicellular organisms for future environmental stresses. Protozoan parasites, such as trypanosomes, face multiple and often hostile environments, and to survive, they undergo multiple changes, including changes in morphology, gene expression, and metabolism. But why does only a subset of proliferative cells differentiate to the next life cycle stage? Why do only some bloodstream parasites undergo antigenic switching while others stably express one variant surface glycoprotein? And why do some parasites invade an organ while others remain in the bloodstream? Building on extensive research performed in bacteria, here we suggest that biological noise can contribute to the fitness of eukaryotic pathogens and discuss the importance of cell-to-cell heterogeneity in trypanosome infections. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Case Study of the Response of N 6 -Methyladenine DNA Modification to Environmental Stressors in the Unicellular Eukaryote Tetrahymena thermophila

mSphere ◽  
2021 ◽  
Author(s):  
Yalan Sheng ◽  
Bo Pan ◽  
Fan Wei ◽  
Yuanyuan Wang ◽  
Shan Gao
Keyword(s):  
Environmental Stress ◽  
Tetrahymena Thermophila ◽  
Environmental Stressors ◽  
Unicellular Eukaryote ◽  
Dna Modification ◽  
Unicellular Eukaryotes ◽  
Unicellular Organisms ◽  
And Function

Increasing evidence indicated that 6mA could respond to environmental stressors in multicellular eukaryotes. As 6mA distribution and function differ significantly in multicellular and unicellular organisms, whether and how 6mA in unicellular eukaryotes responds to environmental stress remains elusive.

Abstract 250: Haploinsufficiency of Muscle-Enriched A-Type Lamin Interacting Protein (MLIP) Manifests as Enlarged Dilated Hearts

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Patrick Burgon ◽  
Julia Lockwood ◽  
Glenn Wells ◽  
Alexandre Blais
Keyword(s):  
Heart Development ◽  
Left Ventricular ◽  
Lamin A ◽  
Interacting Protein ◽  
Cellular Hypertrophy ◽  
Cellular Source ◽  
Alternatively Spliced ◽  
Normal Body Weight ◽  
Heart Size ◽  
And Function

Approximately 116 unique mutations in the lamin A/C gene have been described to date that are associated with dilated cardiomyopathy. We recently reported the discovery of MLIP through its interaction with lamin A/C. MLIP is expressed ubiquitously and most abundantly in heart, skeletal and smooth muscle of amniotes (mammals, reptiles and birds) and has no paralogous homologue suggesting no functional redundancy. The MLIP gene encodes at least seven, alternatively spliced, LMNA-interacting factors that possess several structural motifs not found in any other protein. The MLIP isoforms pattern of expression differs between each of the tissues with heart being the most heterogeneous. Down-regulation of lamin A/C expression by shRNA results in the up-regulation and mis-localization of MLIP. In addition to interacting and co-localizing with lamin A/C we also demonstrated that MLIP localizes to micro-domains in the nucleus with promyelocytic leukemia protein (PML) in close proximity to chromatin. MLIP's biological function still remains elusive. Eight week old hemizygous MLIP null mice develop enlarged hearts with a significant increase in heart to body weights (MLIP+/+ 5.62mg/g vs MLIP+/- 10.73mg/g, p<0.0001 n=7) with an overall 30% increase in the anterior-posterior ventricle length of MLIP hearts while maintaining a normal body weight (Figure). Echocardiographic analysis of MLIP+/- mice revealed that their hearts as having a significant (p3.93mm with a significant (p=0.011, n=12) reduction of left ventricular fractional shorting (LVFS) 31% when compare to littermate controls. Histological analysis of the hearts showed no overt phenotype other than an overall increase in the size of the MLIP+/- hearts. The cellular source for the increase in heart size and mass remains to be determined if it is the product of an increase in the number of cardiomyocytes due to aberrant hyperplasia or an increase in cardiomyocyte size through cellular hypertrophy. In conclusion, MLIP is a newly discovered lamin interacting protein that may serve as a transcriptional regulator that impact genes involved in heart development, growth and function and provides a new signaling paradigm.

Abstract 37: Nrip Deficiency Leads to Dilated Cardiomyopathy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Show-Li Chen
Keyword(s):  
Calcium Transient ◽  
Receptor Interaction ◽  
Cell Width ◽  
Interacting Protein ◽  
Cardiac Tissues ◽  
Calmodulin Binding ◽  
Calcineurin Phosphatase ◽  
And Function

Previously, we demonstrate a gene, nuclear receptor interaction protein (NRIP, also named DCAF6 or IQWD1) as a Ca2+- dependent calmodulin binding protein that can activate calcineurin phosphatase activity. Here, we found that α-actinin-2 (ACTN2), is one of NRIP-interacting proteins from the yeast two-hybrid system using NRIP as a prey. We further confirmed the direct bound between NRIP and ACTN2 using in vitro protein-protein interaction and in vivo co-immunoprecipitation assays. To further map the binding domain of each protein, the results showed the IQ domain of NRIP responsible for ACTN2 binding, and EF hand motif of ACTN2 responsible for NRIP bound. Due to ACTN2 is a biomarker of muscular Z-disc complex; we found the co-localization of NRIP and ACTN2 in cardiac tissues by immunofluorescence assays. Taken together, NRIP is a novel ACTN2-interacting protein. To investigate insights into in vivo function of NRIP, we generated conventional NRIP-null mice. The H&E staining results are shown in the hearts of NRIP KO mice are enlarged and dilated and the cell width of NRIP KO cardiomyocyte is increased. The EM of NRIP KO heart muscles reveal the reduction of I-band width and extension length of Z-disc in sarcomere structure; and the echocardiography shows the diminished fractional shortening in heart functions. Additionally, the calcium transient and sarcomere contraction length in cardiomyocytes of NRIP KO is weaker and shorter than wt; respectively. In conclusion, NRIP is a novel Z-disc protein and has function for maintenance of sarcomere integrity structure and function for calcium transient and muscle contraction.

scholarly journals Evolutionary Conservation of Reactions in Translation

2002 ◽  
Vol 66 (3) ◽  
pp. 460-485 ◽  
Author(s):  
M. Clelia Ganoza ◽  
Michael C. Kiel ◽  
Hiroyuki Aoki
Keyword(s):  
Molecular Mechanisms ◽  
Tertiary Structure ◽  
Evolutionary Conservation ◽  
Initiation Factor ◽  
Structural Studies ◽  
X Ray Diffraction ◽  
X Ray ◽  
Common Features ◽  
New Information ◽  
And Function

SUMMARY Current X-ray diffraction and cryoelectron microscopic data of ribosomes of eubacteria have shed considerable light on the molecular mechanisms of translation. Structural studies of the protein factors that activate ribosomes also point to many common features in the primary sequence and tertiary structure of these proteins. The reconstitution of the complex apparatus of translation has also revealed new information important to the mechanisms. Surprisingly, the latter approach has uncovered a number of proteins whose sequence and/or structure and function are conserved in all cells, indicating that the mechanisms are indeed conserved. The possible mechanisms of a new initiation factor and two elongation factors are discussed in this context.

scholarly journals Expression of Inducible Nitric Oxide Synthase in Skin Lesions of Patients with American Cutaneous Leishmaniasis

2002 ◽  
Vol 70 (8) ◽  
pp. 4638-4642 ◽  
Author(s):  
Muna Qadoumi ◽  
Inge Becker ◽  
Norbert Donhauser ◽  
Martin Röllinghoff ◽  
Christian Bogdan
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Skin Lesions ◽  
And Function ◽  
Oxide Synthase

ABSTRACT Cytokine-inducible (or type 2) nitric oxide synthase (iNOS) is indispensable for the resolution of Leishmania major or Leishmania donovani infections in mice. In contrast, little is known about the expression and function of iNOS in human leishmaniasis. Here, we show by immunohistological analysis of skin biopsies from Mexican patients with local (LCL) or diffuse (DCL) cutaneous leishmaniasis that the expression of iNOS was most prominent in LCL lesions with small numbers of parasites whereas lesions with a high parasite burden (LCL or DCL) contained considerably fewer iNOS-positive cells. This is the first study to suggest an antileishmanial function of iNOS in human Leishmania infections in vivo.

Probing the Structure and Function of Human Glutaminase-Interacting Protein: A Possible Target for Drug Design†‡

Biochemistry ◽  
2008 ◽  
Vol 47 (35) ◽  
pp. 9208-9219 ◽  
Author(s):  
Monimoy Banerjee ◽  
Chengdong Huang ◽  
Javier Marquez ◽  
Smita Mohanty
Keyword(s):  
Drug Design ◽  
Protein A ◽  
Structure And Function ◽  
Interacting Protein ◽  
And Function

scholarly journals A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2

2020 ◽  
Vol 21 (6) ◽  
pp. 2054
Author(s):  
Anton A. Komar ◽  
William C. Merrick
Keyword(s):  
Translational Control ◽  
Ribosomal Subunit ◽  
Initiation Factor ◽  
Single Chain ◽  
Initiation Factors ◽  
Eif2α Phosphorylation ◽  
Specific Mrnas ◽  
Internal Initiation ◽  
And Function ◽  
Polypeptide Chains

Initiation of protein synthesis in eukaryotes is a complex process requiring more than 12 different initiation factors, comprising over 30 polypeptide chains. The functions of many of these factors have been established in great detail; however, the precise role of some of them and their mechanism of action is still not well understood. Eukaryotic initiation factor 2A (eIF2A) is a single chain 65 kDa protein that was initially believed to serve as the functional homologue of prokaryotic IF2, since eIF2A and IF2 catalyze biochemically similar reactions, i.e., they stimulate initiator Met-tRNAi binding to the small ribosomal subunit. However, subsequent identification of a heterotrimeric 126 kDa factor, eIF2 (α,β,γ) showed that this factor, and not eIF2A, was primarily responsible for the binding of Met-tRNAi to 40S subunit in eukaryotes. It was found however, that eIF2A can promote recruitment of Met-tRNAi to 40S/mRNA complexes under conditions of inhibition of eIF2 activity (eIF2α-phosphorylation), or its absence. eIF2A does not function in major steps in the initiation process, but is suggested to act at some minor/alternative initiation events such as re-initiation, internal initiation, or non-AUG initiation, important for translational control of specific mRNAs. This review summarizes our current understanding of the eIF2A structure and function.

ARL1 has an essential role in Trypanosoma brucei

2005 ◽  
Vol 33 (4) ◽  
pp. 643-645 ◽  
Author(s):  
H.P. Price ◽  
D. Goulding ◽  
D.F. Smith
Keyword(s):  
Trypanosoma Brucei ◽  
Leishmania Major ◽  
Growth Arrest ◽  
Surface Glycoprotein ◽  
Cellular Proteins ◽  
Protozoan Parasites ◽  
Range Of Functions ◽  
Golgi Structure ◽  
Adp Ribosylation Factor ◽  
Myristoyl Coa

Myristoyl-CoA protein:NMT (N-myristoyl transferase) catalyses the N-myristoylation of cellular proteins with a range of functions and is essential for viability in the protozoan parasites, Leishmania major and Trypanosoma brucei. In our investigations to define the essential downstream targets of NMT, we have focused on the ARF (ADP-ribosylation factor) family of proteins, as growth arrest in Saccharomyces cerevisiae mutants with reduced NMT activity correlates with decreased modification of members of this group of proteins. We have identified nine ARF/ARLs (where ARL stands for ARF-like) encoded in the T. brucei and T. cruzi genomes and ten in L. major. The T. brucei ARL1 protein is expressed only in the mammalian bloodstream form of the parasite, in which it is localized to the Golgi apparatus. RNAi (RNA interference) has been used to demonstrate that ARL1 is essential for viability in these infective cells. Before cell death, depletion of ARL1 protein results in disintegration of the Golgi structure and a delay in exocytosis of the abundant GPI (glycosylphosphatidylinositol)-anchored VSG (variant surface glycoprotein) to the parasite surface.

scholarly journals Autophagy in unicellular eukaryotes

2010 ◽  
Vol 365 (1541) ◽  
pp. 819-830 ◽  
Author(s):  
Jan A. K. W. Kiel
Keyword(s):  
Molecular Mechanisms ◽  
Yeast Species ◽  
Developmental Change ◽  
Building Blocks ◽  
Extracellular Medium ◽  
New Host ◽  
Growth And Survival ◽  
Atp Production ◽  
Unicellular Eukaryotes

Cells need a constant supply of precursors to enable the production of macromolecules to sustain growth and survival. Unlike metazoans, unicellular eukaryotes depend exclusively on the extracellular medium for this supply. When environmental nutrients become depleted, existing cytoplasmic components will be catabolized by (macro)autophagy in order to re-use building blocks and to support ATP production. In many cases, autophagy takes care of cellular housekeeping to sustain cellular viability. Autophagy encompasses a multitude of related and often highly specific processes that are implicated in both biogenetic and catabolic processes. Recent data indicate that in some unicellular eukaryotes that undergo profound differentiation during their life cycle (e.g. kinetoplastid parasites and amoebes), autophagy is essential for the developmental change that allows the cell to adapt to a new host or form spores. This review summarizes the knowledge on the molecular mechanisms of autophagy as well as the cytoplasm-to-vacuole-targeting pathway, pexophagy, mitophagy, ER-phagy, ribophagy and piecemeal microautophagy of the nucleus, all highly selective forms of autophagy that have first been uncovered in yeast species. Additionally, a detailed analysis will be presented on the state of knowledge on autophagy in non-yeast unicellular eukaryotes with emphasis on the role of this process in differentiation.

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