scholarly journals Moving toward molecular mechanisms for chemotaxis in eukaryotic cells

2019 ◽  
Vol 30 (23) ◽  
pp. 2873-2877
Author(s):  
Peter Devreotes
Keyword(s):  
Molecular Mechanisms ◽  
Eukaryotic Cells ◽  
To Receive

It is a tremendous honor to receive the 2019 E.B. Wilson Award and be recognized for my work on chemotaxis in eukaryotic cells. In writing this essay, I hope to achieve three aims: 1) to tell the story of how people in my group made discoveries over the years; 2) to outline key principles we have learned about chemotaxis; and 3) to point to the most important outstanding questions.

scholarly journals Mitochondrial Dynamics, ROS, and Cell Signaling: A Blended Overview

Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 332
Author(s):  
Valentina Brillo ◽  
Leonardo Chieregato ◽  
Luigi Leanza ◽  
Silvia Muccioli ◽  
Roberto Costa
Keyword(s):  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Eukaryotic Cells ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Lipid Trafficking ◽  
Mitochondrial Ros ◽  
Intracellular Organelles ◽  
Proliferation Regulation ◽  
Dynamic Plasticity

Mitochondria are key intracellular organelles involved not only in the metabolic state of the cell, but also in several cellular functions, such as proliferation, Calcium signaling, and lipid trafficking. Indeed, these organelles are characterized by continuous events of fission and fusion which contribute to the dynamic plasticity of their network, also strongly influenced by mitochondrial contacts with other subcellular organelles. Nevertheless, mitochondria release a major amount of reactive oxygen species (ROS) inside eukaryotic cells, which are reported to mediate a plethora of both physiological and pathological cellular functions, such as growth and proliferation, regulation of autophagy, apoptosis, and metastasis. Therefore, targeting mitochondrial ROS could be a promising strategy to overcome and hinder the development of diseases such as cancer, where malignant cells, possessing a higher amount of ROS with respect to healthy ones, could be specifically targeted by therapeutic treatments. In this review, we collected the ultimate findings on the blended interplay among mitochondrial shaping, mitochondrial ROS, and several signaling pathways, in order to contribute to the dissection of intracellular molecular mechanisms involved in the pathophysiology of eukaryotic cells, possibly improving future therapeutic approaches.

scholarly journals Membrane Repair: Mechanisms and Pathophysiology

2015 ◽  
Vol 95 (4) ◽  
pp. 1205-1240 ◽  
Author(s):  
Sandra T. Cooper ◽  
Paul L. McNeil
Keyword(s):  
Molecular Mechanisms ◽  
Eukaryotic Cells ◽  
Membrane Repair ◽  
Membrane Pore ◽  
Rapid Repair ◽  
Repair Mechanisms ◽  
Molecular Machinery ◽  
Repair Pathways ◽  
Different Tissues ◽  
Ischemic Stress

Eukaryotic cells have been confronted throughout their evolution with potentially lethal plasma membrane injuries, including those caused by osmotic stress, by infection from bacterial toxins and parasites, and by mechanical and ischemic stress. The wounded cell can survive if a rapid repair response is mounted that restores boundary integrity. Calcium has been identified as the key trigger to activate an effective membrane repair response that utilizes exocytosis and endocytosis to repair a membrane tear, or remove a membrane pore. We here review what is known about the cellular and molecular mechanisms of membrane repair, with particular emphasis on the relevance of repair as it relates to disease pathologies. Collective evidence reveals membrane repair employs primitive yet robust molecular machinery, such as vesicle fusion and contractile rings, processes evolutionarily honed for simplicity and success. Yet to be fully understood is whether core membrane repair machinery exists in all cells, or whether evolutionary adaptation has resulted in multiple compensatory repair pathways that specialize in different tissues and cells within our body.

scholarly journals Protein Machineries Involved in the Attachment of Heme to Cytochrome c: Protein Structures and Molecular Mechanisms

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
Carlo Travaglini-Allocatelli
Keyword(s):  
Molecular Mechanisms ◽  
Protein Structures ◽  
Eukaryotic Cells ◽  
Binding Motif ◽  
Gram Negative ◽  
Open Questions ◽  
Structural And Functional Properties ◽  
Cyt C ◽  
Electron Transfer Processes ◽  
Cysteine Thiols

Cytochromes c (Cyt c) are ubiquitous heme-containing proteins, mainly involved in electron transfer processes, whose structure and functions have been and still are intensely studied. Surprisingly, our understanding of the molecular mechanism whereby the heme group is covalently attached to the apoprotein (apoCyt) in the cell is still largely unknown. This posttranslational process, known as Cyt c biogenesis or Cyt c maturation, ensures the stereospecific formation of the thioether bonds between the heme vinyl groups and the cysteine thiols of the apoCyt heme binding motif. To accomplish this task, prokaryotic and eukaryotic cells have evolved distinctive protein machineries composed of different proteins. In this review, the structural and functional properties of the main maturation apparatuses found in gram-negative and gram-positive bacteria and in the mitochondria of eukaryotic cells will be presented, dissecting the Cyt c maturation process into three functional steps: (i) heme translocation and delivery, (ii) apoCyt thioreductive pathway, and (iii) apoCyt chaperoning and heme ligation. Moreover, current hypotheses and open questions about the molecular mechanisms of each of the three steps will be discussed, with special attention to System I, the maturation apparatus found in gram-negative bacteria.

scholarly journals Molecular Basis of Tubulin Transport Within the Cilium by IFT74 and IFT81

Science ◽  
2013 ◽  
Vol 341 (6149) ◽  
pp. 1009-1012 ◽  
Author(s):  
Sagar Bhogaraju ◽  
Lukas Cajanek ◽  
Cécile Fort ◽  
Thierry Blisnick ◽  
Kristina Weber ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Intraflagellar Transport ◽  
Human Cells ◽  
Eukaryotic Cells ◽  
Calponin Homology Domain ◽  
Basic Domain ◽  
Calponin Homology ◽  
Tubulin Binding

Intraflagellar transport (IFT) of ciliary precursors such as tubulin from the cytoplasm to the ciliary tip is involved in the construction of the cilium, a hairlike organelle found on most eukaryotic cells. However, the molecular mechanisms of IFT are poorly understood. Here, we found that the two core IFT proteins IFT74 and IFT81 form a tubulin-binding module and mapped the interaction to a calponin homology domain of IFT81 and a highly basic domain in IFT74. Knockdown of IFT81 and rescue experiments with point mutants showed that tubulin binding by IFT81 was required for ciliogenesis in human cells.

scholarly journals Interaction of bacterial extracellular microvesicles with eukaryotic cells.

2021 ◽  
Vol 22 (6) ◽  
pp. 1065-1084
Author(s):  
D. S. Shlykova ◽  
V. M. Pisarev ◽  
A. M. Gaponov ◽  
A. V. Tutelyan
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Inflammatory Cytokines ◽  
Human Body ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Signal Molecules ◽  
Opportunistic Bacteria ◽  
Cytokines Secretion

Bacterial extracellular microvesicles (BMV) are formed by nonpathogenic, pathogenic and opportunistic bacteria. BMV are spherical bilayer-membrane organelles containing different cargoes: lipopolysaccharides, pathogen associated molecular patterns (PUMP), DNA, RNA, signal molecules, proteins, antibiotic resistance factors, virulence factors, toxins providing various immune response options and conducive to the survival and pathogen dissemination in the human body. BMVs secretion play an important role in the ability of microorganisms to cause various diseases. BMV are involved in biofilms formation, help bacteria to obtain nutrition in a nutrient-poor conditions, to evade the host's immune response, provide communication and surviving in a stressful environment during infection inside the host. The heterogeneity of the biogenesis mechanisms causes differences in the BMV and their characteristics including virulence rate. BMVs host cells entering is mediated by several mechanisms and helps to activate innate and adaptive immune reactions. This review focuses on interaction study of BMV with various eukaryotic cells types including neutrophils, dendritic cells, macrophages, epithelial, endothelial cells. This interaction depends on bacteria species, type of target cell and number of vesicles and can lead to different responses: non-immunogenic, pro-inflammatory, cytotoxic. Subcellular and molecular mechanisms related to the involvement of extracellular microvesicles in host's immune response modulation are presented. Stimulation of immune response is provided by increased secretion of proinflammatory cytokines and chemokines. In some cases BMV use mechanisms to evade immune surveillance: anti-inflammatory cytokines secretion, alterations of phagocytosis and chemotaxis of macrophages, increasing the proteolytic cleavage of CD14 on the macrophage surface, alterations of antigen-presenting function of dendritic cells, T-cell proliferation suppression, reducing the pro-inflammatory cytokines secretion, evasion of host-immune cells direct interactions, destruction of neutrophilic traps. These features allow bacterial cells to survive in the human body, increase their invasive potential, and reduce the excessive inflammatory reactions leading to death of the pathogen itself and life-threatening damage of tissues and organs of the host. Further studies of these mechanisms will improve existing therapeutic approaches to the infectious diseases treatment.

scholarly journals Exocytosis in Astrocytes

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1367
Author(s):  
Aleksandra Mielnicka ◽  
Piotr Michaluk
Keyword(s):  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Brain Metabolism ◽  
Eukaryotic Cells ◽  
Regulated Exocytosis

Until recently, astrocytes were thought to be a part of a simple “brain glue” providing only a supporting role for neurons. However, the discoveries of the last two decades have proven astrocytes to be dynamic partners participating in brain metabolism and actively influencing communication between neurons. The means of astrocyte-neuron communication are diverse, although regulated exocytosis has received the most attention but also caused the most debate. Similar to most of eukaryotic cells, astrocytes have a complex range of vesicular organelles which can undergo exocytosis as well as intricate molecular mechanisms that regulate this process. In this review, we focus on the components needed for regulated exocytosis to occur and summarise the knowledge about experimental evidence showing its presence in astrocytes.

scholarly journals Proteasome autophagy is specifically regulated and requires factors dispensible for general autophagy

2021 ◽  
Author(s):  
Kenrick A. Waite ◽  
Alicia Burris ◽  
Gabrielle Vontz ◽  
Angelica Lang ◽  
Jeroen Roelofs
Keyword(s):  
Map Kinases ◽  
Molecular Mechanisms ◽  
Ubiquitin Proteasome System ◽  
Molecular Regulation ◽  
Eukaryotic Cells ◽  
Phasic Response ◽  
Selective Autophagy ◽  
Physiological Conditions ◽  
Ubiquitin Proteasome ◽  
Chemical Inhibition

ABSTRACTChanging physiological conditions can increase the need for protein degradative capacity in eukaryotic cells. Both the ubiquitin-proteasome system and autophagy contribute to protein degradation. However, proteasomes are also an autophagy substrate. Thus, these processes must be differentially regulated depending on the physiological conditions presented. The signals and molecular mechanisms that govern proteasome autophagy are only partly elucidated. Our data indicate that chemical inhibition of TORC1 with rapamycin induces a bi-phasic response where proteasome levels are upregulated followed by an autophagy-dependent reduction. Surprisingly, several conditions that result in inhibited TORC1 exclusively induce proteasome autophagy (i.e. without any proteasome upregulation), suggesting a convergence of signals upstream of proteasome autophagy under different physiological conditions. Indeed, several conditions that activate general autophagy did not induce proteasome autophagy further distinguishing between proteasome autophagy and general autophagy. Consistent with this, we found that Atg11, the receptor for selective autophagy, and the map kinases Mpk1, Mkk1, and Mkk2, all play a role in autophagy of proteasomes, while they are dispensible for general autophagy. In all, our data provide new insights into the molecular regulation of proteasome autophagy by demonstrating that these complexes are specifically regulated under different autophagy inducing conditions.

scholarly journals A piggybacking mechanism enables peroxisomal localization of the glyoxylate cycle enzyme Mdh2 in yeast

2020 ◽  
pp. jcs.244376
Author(s):  
Shiran Gabay-Maskit ◽  
Luis Daniel Cruz-Zaragoza ◽  
Nadav Shai ◽  
Miriam Eisenstein ◽  
Chen Bibi ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Glyoxylate Cycle ◽  
Eukaryotic Cells ◽  
Cycle Enzyme ◽  
Dual Localization ◽  
Temporal And Spatial ◽  
New Perspective ◽  
The Glyoxylate Cycle

Eukaryotic cells evolved organelles that allow the compartmentalization and regulation of metabolic processes. Knowledge on molecular mechanisms that allow temporal and spatial organization of enzymes within organelles is therefore critical for understanding eukaryotic metabolism. Here we show that the yeast malate dehydrogenase 2 (Mdh2) is dually localized to the cytosol and to peroxisomes and is targeted to peroxisomes via association with Mdh3 and a Pex5-dependent piggybacking mechanism. The dual localization of Mdh2 contributes to our understanding of the glyoxylate cycle and provides a new perspective on compartmentalization of cellular metabolism, which is critical for the perception of metabolic disorders and aging.

scholarly journals The Phospholipid Profile of Mycoplasmas

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jonathan D. Kornspan ◽  
Shlomo Rottem
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Inflammatory Responses ◽  
Polar Lipids ◽  
Host Cells ◽  
Eukaryotic Cells ◽  
Ether Lipids ◽  
Mycoplasma Cell ◽  
Phospholipid Profile

Thede novosynthesized polar lipids ofMycoplasmaspecies are rather simple, comprising primarily of the acidic glycerophospholipids PG and CL. In addition, when grown in a medium containing serum, significant amounts of PC and SPM are incorporated into the mycoplasma cell membrane although these lipids are very uncommon in wall-covered bacteria. The exogenous lipids are either incorporated unchanged or the PC incorporated is modified by a deacylation-acylation enzymatic cycle to form disaturated PC. Although their small genome, in someMycoplasmaspecies, other genes involved in lipid biosynthesis were detected, resulting in the synthesis of a variety of glycolipis, phosphoglycolipids and ether lipids. We suggest that analyses and comparisons of mycoplasma polar lipids may serve as a novel and useful tool for classification. Nonetheless, to evaluate the importance of polar lipids in mycoplasma, further systematic and extensive studies on moreMycoplasmaspecies are needed. While studies are needed to elucidate the role of lipids in the mechanisms governing the interaction of mycoplasmas with host eukaryotic cells, the finding that a terminal phosphocholine containing glycolipids ofM. fermentansserves both as a major immune determinants and as a trigger of the inflammatory responses, and the findings that the fusogenicity ofM. fermentanswith host cells is markedly stimulated by lyso-ether lipids, are important steps toward understanding the molecular mechanisms ofM. fermentanspathogenicity.

A novel function of lipid droplets in regulating longevity

2009 ◽  
Vol 37 (5) ◽  
pp. 1050-1055 ◽  
Author(s):  
Alexander A. Goldberg ◽  
Simon D. Bourque ◽  
Pavlo Kyryakov ◽  
Tatiana Boukh-Viner ◽  
Christopher Gregg ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Aging Process ◽  
Essential Role ◽  
Molecular Mechanisms ◽  
Neutral Lipids ◽  
Intracellular Signalling ◽  
Eukaryotic Cells ◽  
Eukaryotic Organisms

Growing evidence supports the view that LDs (lipid droplets) are dynamic organelles that can serve both as an intracellular signalling compartment and as an organizing platform orchestrating many vital processes in eukaryotic cells. It has become clear that the LDs-confined deposition and lipolytic degradation of neutral lipids define longevity in multicellular eukaryotic organisms and yeast. We summarize the evidence in support of the essential role that LDs play in longevity regulation and propose several molecular mechanisms by which these dynamic organellar compartments control the aging process in multicellular eukaryotes and yeast.

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