scholarly journals The novel Rab5 effector FERRY links early endosomes with the translation machinery

2021 ◽  
Author(s):  
Jan S Schuhmacher ◽  
Susanne tom Dieck ◽  
Savvas Christoforidis ◽  
Cedric Landerer ◽  
Lena Hersemann ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Mrna Localization ◽  
Mitochondrial Proteins ◽  
The Novel ◽  
Translation Machinery ◽  
Early Endosomes ◽  
Close Proximity ◽  
Polarized Cells ◽  
Entire Cell ◽  
Underlying Mechanisms

Local translation is vital to polarized cells such as neurons and requires a precise and robust distribution of different mRNAs and the translation machinery across the entire cell. The underlying mechanisms are poorly understood and important players are still to be identified. Here, we discovered a novel Rab5 effector complex which leads to mental retardation when genetically disrupted. The Five-subunit Endosomal Rab5 and RNA/ribosome intermediarY, FERRY complex localizes to early endosomes and associates with the translation machinery and a subset of mRNAs including mRNAs for mitochondrial proteins. It directly interacts with mRNA, thereby exhibiting different binding efficacies. Deletion of FERRY subunits reduces the endosomal localization of transcripts, indicating a role in mRNA distribution. Accordingly, FERRY-positive early endosomes harboring mRNA encoding mitochondrial proteins were observed in close proximity to mitochondria in neurons. Therefore, the FERRY complex plays a role for mRNA localization by linking early endosomes with the translation machinery.

scholarly journals Hop-on hop-off: Polysomes take a tour of the cell on endosomes

2014 ◽  
Vol 204 (3) ◽  
pp. 287-289 ◽  
Author(s):  
Isabel M. Palacios
Keyword(s):  
Protein Synthesis ◽  
Long Range ◽  
Ustilago Maydis ◽  
Hyphal Cell ◽  
Translation Machinery ◽  
Cell Biol ◽  
Early Endosomes ◽  
Entire Cell ◽  
Bidirectional Movement

After export from the nucleus, ribosomes need to be distributed throughout the entire cell so that protein synthesis can occur even at distant sites. In the elongated hyphal cell of the fungus Ustilago maydis, Higuchi et al. (2014. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201307164) now demonstrate that polysomes associate with early endosomes that undergo kinesin 3– and dynein-dependent long-range motility. The bidirectional movement of early endosomes randomly distributes polysomes, which may ensure the even distribution of the translation machinery across the entire cell.

scholarly journals The Novel Rab5 Effector FERRY Links Early Endosomes With the Translation Machinery

2021 ◽  
Author(s):  
Jan S. Schuhmacher ◽  
Susanne tom Dieck ◽  
Savvas Christoforidis ◽  
Cedric Landerer ◽  
Lena Hersemann ◽  
...  
Keyword(s):  
The Novel ◽  
Translation Machinery ◽  
Early Endosomes

scholarly journals The preendosomal compartment comprises distinct coated and noncoated endocytic vesicle populations.

1991 ◽  
Vol 113 (4) ◽  
pp. 731-741 ◽  
Author(s):  
S H Hansen ◽  
K Sandvig ◽  
B van Deurs
Keyword(s):  
Cell Surface ◽  
Coated Vesicles ◽  
Minor Role ◽  
Specific Marker ◽  
Con A ◽  
Early Endosomes ◽  
Gold Conjugate ◽  
Entire Cell ◽  
A Minor ◽  
Endocytic Vesicles

The transfer of molecules from the cell surface to the early endosomes is mediated by preendosomal vesicles. These vesicles, which have pinched off completely from the plasma membrane but not yet fused with endosomes, form the earliest compartment along the endocytic route. Using a new assay to distinguish between free and cell surface connected vesicle profiles, we have characterized the preedosomal compartment ultrastructurally. Our basic experimental setup was labeling of the entire cell surface at 4 degrees C with Con A-gold, warming of the cells to 37 degrees C to allow endocytosis, followed by replacing incubation medium with fixative, all within either 30 or 60 s. Then the fixed cells were incubated with anti-Con A-HRP to distinguish truly free (gold labeled) endocytic vesicles from surface-connected structures. Finally, analysis of thin (20-30 nm) serial sections and quantification of vesicle diameters were carried out. Based on this approach it is shown that the preendosomal compartment comprises both clathrin-coated and non-coated endocytic vesicles with approximately the same frequency but with distinct diameter distributions, the average noncoated vesicle being smaller (95 nm) than the average coated one (110 nm). In parallel experiments, using an anti-transferrin receptor gold-conjugate as a specific marker for clathrin-dependent endocytosis it is also shown that uncoating of coated vesicles plays only a minor role for the total frequency of noncoated vesicles. Furthermore, after perturbation of clathrin-dependent endocytosis by potassium depletion where uptake of transferrin is blocked, noncoated endocytic vesicles with Con A-gold, but not coated vesicles, exist already after 30 and 60 s. Finally, it is shown that the existence of small, free vesicles in the short-time experiments cannot be ascribed to recycling from the early endosomes.

Disruptions of the novel KIAA1202 gene are associated with X-linked mental retardation

2005 ◽  
Vol 118 (5) ◽  
pp. 578-590 ◽  
Author(s):  
Olivier Hagens ◽  
Aline Dubos ◽  
Fatima Abidi ◽  
Gotthold Barbi ◽  
Laura Van Zutven ◽  
...  
Keyword(s):  
Mental Retardation ◽  
The Novel

scholarly journals Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

2018 ◽  
Vol 50 (6) ◽  
pp. 2390-2405 ◽  
Author(s):  
Shuping Wei ◽  
Jingjing Zhang ◽  
Biao Han ◽  
Jianxun Liu ◽  
Xiaohui Xiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Zinc Finger ◽  
Erk Signaling ◽  
The Novel ◽  
Differentiation Markers ◽  
Zinc Finger Transcription Factor ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Injury Model ◽  
Underlying Mechanisms

Background/Aims: Phenotypic switching of vascular smooth muscle cells (VSMC) plays a vital role in the development of vascular diseases. All-trans retinoic acid (ATRA) is known to regulate VSMC phenotypes. However, the underlying mechanisms remain completely unknown. Here, we have investigated the probable roles and underlying mechanisms of the novel C2H2 zinc finger transcription factor ZFP580 on ATRA-induced VSMC differentiation. Methods: VSMCs were isolated, cultured, and identified. VSMCs were infected with an adenovirus encoding ZFP580 or Ad-siRNA to silence ZFP580. The expression levels of ZFP580, SMα-actin, SM22α, SMemb, RARα, RARβ, and RARγ were assayed by Q-PCR and western blot. A rat carotid artery injury model and morphometric analysis of intimal thickening were also used in this study. Results: ATRA caused a significant reduction of VSMC proliferation and migration in a doseand time-dependent manner. Moreover, it promoted VSMC differentiation by enhancing expression of differentiation markers and reducing expression of dedifferentiation markers. This ATRA activity was accompanied by up-regulation of ZFP580, with concomitant increases in RARα expression. In contrast, silencing of the RARα gene or inhibiting RARα with its antagonist Ro41-5253 abrogated the ATRA-induced ZFP580 expression. Furthermore, ATRA binding to RARα induced ZFP580 expression via the PI3K/Akt and ERK pathways. Adenovirusmediated overexpression of ZFP580 promoted VSMC differentiation by enhancing expression of SM22α and SMα-actin and reducing expression of SMemb. In contrast, silencing ZFP580 dramatically reduced the expression of differentiation markers and increased expression of dedifferentiation markers. The classic rat carotid artery balloon injury model demonstrated that ZFP580 inhibited proliferation and intimal hyperplasia in vivo. Conclusion: The novel zinc finger transcription factor ZFP580 facilitates ATRA-induced VSMC differentiation by the RARα-mediated PI3K/Akt and ERK signaling pathways. This might represent a novel mechanism of regulation of ZFP580 by ATRA and RARα, which is critical for understanding the biological functions of retinoids during VSMC phenotypic modulation.

scholarly journals Molecular edge effects in the Endangered golden-brown mouse lemur Microcebus ravelobensis

Oryx ◽  
2018 ◽  
Vol 53 (4) ◽  
pp. 716-726 ◽  
Author(s):  
U. Radespiel ◽  
J. Schulte ◽  
R. J. Burke ◽  
S. M. Lehman
Keyword(s):  
Edge Effects ◽  
Deciduous Forest ◽  
Mitochondrial Control Region ◽  
Mouse Lemur ◽  
Continuous Forest ◽  
Ecological Changes ◽  
Close Proximity ◽  
Geographical Distances ◽  
Dry Deciduous Forest ◽  
Underlying Mechanisms

AbstractHabitat fragmentation creates habitat edges, and ecological edge effects can cause major changes in the ecology and distribution of many taxa. However, these ecological changes may in turn influence animal movements and lead to molecular edge effects and edge-related genetic structure, matters that are largely unexplored. This study aims to infer molecular edge effects and to test three possible underlying mechanisms in the Endangered golden-brown mouse lemur Microcebus ravelobensis, a nocturnal species in the dry deciduous forest of the Ankarafantsika National Park in north-western Madagascar. Mouse lemurs were sampled in one edge and two interior habitats in close proximity to each other (500–1,400 m) in a continuous forest. A total of 41 mouse lemur samples were genotyped with seven nuclear microsatellites, and a fragment of the mitochondrial control region was sequenced for all samples. The overall genetic diversity (allelic richness, heterozygosity, haplotype richness, nucleotide diversity) was lower in the edge habitat compared to the two interior sites and all subpopulations showed signals of relatively low genetic exchange and significant genetic differentiation between them despite the short geographical distances, supporting the local preference model. These findings can be interpreted as preliminary signals of a molecular edge effect and suggest the potential for local adaptation. They are highly relevant for the conservation of fragmented populations, because a further subdivision of already small populations may increase their vulnerability to stochastic demographic changes and collapse.

scholarly journals A critical role of the T3SS effector EseJ in intracellular trafficking and replication ofEdwardsiella piscicidain non-phagocytic cells

2018 ◽  
Author(s):  
Lingzhi Zhang ◽  
Jiatiao Jiang ◽  
Tianjian Hu ◽  
Jin Zhang ◽  
Xiaohong Liu ◽  
...  
Keyword(s):  
Bacterial Colonization ◽  
Critical Role ◽  
Host Cells ◽  
Intracellular Replication ◽  
Phagocytic Cells ◽  
T3ss Effector ◽  
Early Endosomes ◽  
Underlying Mechanisms ◽  
Endosome Maturation

AbstractEdwardsiella piscicida(E. piscicida) is an intracellular pathogen within a broad spectrum of hosts. Essential toE. piscicidavirulence is its ability to survive and replicate inside host cells, yet the underlying mechanisms and the nature of the replicative compartment remain unclear. Here, we characterized its intracellular lifestyle in non-phagocytic cells and showed that intracellular replication ofE. piscicidain non-phagocytic cells is dependent on its type III secretion system. Following internalization,E. piscicidais contained in vacuoles that transiently mature into early endosomes, but subsequently bypasses the classical endosome pathway and fusion with lysosomes which depends on its T3SS. Following a rapid escape from the degradative pathway,E. piscicidawas found to create a specialized replication-permissive niche characterized by endoplasmic reticulum (ER) markers. We also found that a T3SS effector EseJ is responsible for intracellular replication ofE. piscicidaby preventing endosome/lysosome fusion. Furthermore,in vivoexperiments confirmed that EseJ is necessary for bacterial colonization ofE. piscicidain both mice and zebrafish. Thus, this work elucidates the strategies used byE. piscicidato survive and proliferate within host non-phagocytic cells.Author summaryE. piscicidais a facultative intracellular bacterium associated with septicemia and fatal infections in many animals, including fish and humans. However, little is known about its intracellular life, which is important for successful invasion of the host. The present study is the first comprehensive characterization ofE. piscicida’s intracellular life-style in host cells. Upon internalization,E. piscicidais transiently contained in Rab5-positive vacuoles, but the pathogen prevents further endosome maturation and fusion with lysosomes by utilizing an T3SS effector EseJ. In addition, the bacterium creates an specialized replication niche for rapid growth via an interaction with the ER. Our study provides new insights into the strategies used byE. piscicidato successfully establishes an intracellular lifestyle that contributes to its survival and dissemination during infection.

scholarly journals Peroxisomes move by hitchhiking on early endosomes using the novel linker protein PxdA

2015 ◽  
Author(s):  
John Salogiannis ◽  
Martin J. Egan ◽  
Samara L. Reck-Peterson
Keyword(s):  
Molecular Motors ◽  
Intracellular Transport ◽  
Coiled Coil ◽  
Leading Edge ◽  
Time Lapse ◽  
Early Endosome ◽  
Organelle Transport ◽  
The Novel ◽  
Coiled Coil Region ◽  
Early Endosomes

Eukaryotic cells use microtubule-based intracellular transport for the delivery of many subcellular cargos, including organelles. The canonical view of organelle transport is that organelles directly recruit molecular motors via cargo-specific adaptors. In contrast to this view, we show here that peroxisomes move by hitchhiking on early endosomes, an organelle that directly recruits the transport machinery. Using the filamentous fungus Aspergillus nidulans we find that hitchhiking is mediated by a novel endosome-associated linker protein, PxdA. PxdA is required for normal distribution and long-range movement of peroxisomes, but not early endosomes or nuclei. Using simultaneous time-lapse imaging we find that early endosome-associated PxdA localizes to the leading edge of moving peroxisomes. We identify a coiled-coil region within PxdA that is necessary and sufficient for early endosome localization and peroxisome distribution and motility. These results present a new mechanism of microtubule-based organelle transport where peroxisomes hitchhike on early endosomes and identify PxdA as the novel linker protein required for this coupling.

Transient Response of Laminated Plates Subject to Close Proximity Explosions

1999 ◽  
Author(s):  
John M. Coggin ◽  
Jeffrey M. K. Chock ◽  
Rakesh K. Kapania ◽  
Eric R. Johnson
Keyword(s):  
Transient Response ◽  
Composite Plates ◽  
Laminated Plates ◽  
Blast Load ◽  
The Novel ◽  
Element Mesh ◽  
Simply Supported ◽  
First Order ◽  
Close Proximity ◽  
Load Types

Abstract We study the transient response of simply supported composite plates subject to close proximity explosions. Many studies are currently availiable in which the blast load is applied uniformly across the plate; and is described by step, N-pulse, or Friedlander equations. The novel aspect considered here is the case for which the blast pressure is due to a close proximity explosion, and is therefore taken to be both spatially and temporally varying. Two methods for calculating blast pressures are developed for arbitrary blast size and distance. A FORTAN program is described that automates the application of an arbitrary blast load to a generic finite element mesh. Modal superposition and NASTRAN solution procedures are verified for several load types and stacking sequences. Results are obtained within the framework of classical and first order plate theories for a variety of parameters including; stacking sequence, blast size, blast distance, and blast calculation method.

scholarly journals The Emerging Role of GC-MSCs in the Gastric Cancer Microenvironment: From Tumor to Tumor Immunity

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhaoji Pan ◽  
Yiqing Tian ◽  
Guoping Niu ◽  
Chengsong Cao
Keyword(s):  
Gastric Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Wound Repair ◽  
Critical Role ◽  
The Novel ◽  
Potential Biomarker ◽  
Underlying Mechanisms ◽  
Gastric Cancer Progression

Mesenchymal stem cells (MSCs) have been declared to not only participate in wound repair but also affect tumor progression. Tumor-associated MSCs, directly existing in the tumor microenvironment, play a critical role in tumor initiation, progression, and development. And different tumor-derived MSCs have their own unique characteristics. In this review, we mainly describe and discuss recent advances in our understanding of the emerging role of gastric cancer-derived MSC-like cells (GC-MSCs) in regulating gastric cancer progression and development, as well as the bidirectional influence between GC-MSCs and immune cells of the tumor microenvironment. Moreover, we also discuss the potential biomarker and therapeutic role of GC-MSCs. It is anticipated that new and deep insights into the functionality of GC-MSCs and the underlying mechanisms will promote the novel and promising therapeutic strategies against gastric cancer.

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