scholarly journals Cellular and molecular actors of myeloid cell fusion: podosomes and tunneling nanotubes call the tune

2021 ◽  
Author(s):  
Ophélie Dufrançais ◽  
Rémi Mascarau ◽  
Renaud Poincloux ◽  
Isabelle Maridonneau-Parini ◽  
Brigitte Raynaud-Messina ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Myeloid Cell ◽  
Giant Cells ◽  
Current Status ◽  
Bone Homeostasis ◽  
Cellular Mechanisms ◽  
Tunneling Nanotubes ◽  
Surface Receptors ◽  
Cell To Cell Adhesion

AbstractDifferent types of multinucleated giant cells (MGCs) of myeloid origin have been described; osteoclasts are the most extensively studied because of their importance in bone homeostasis. MGCs are formed by cell-to-cell fusion, and most types have been observed in pathological conditions, especially in infectious and non-infectious chronic inflammatory contexts. The precise role of the different MGCs and the mechanisms that govern their formation remain poorly understood, likely due to their heterogeneity. First, we will introduce the main populations of MGCs derived from the monocyte/macrophage lineage. We will then discuss the known molecular actors mediating the early stages of fusion, focusing on cell-surface receptors involved in the cell-to-cell adhesion steps that ultimately lead to multinucleation. Given that cell-to-cell fusion is a complex and well-coordinated process, we will also describe what is currently known about the evolution of F-actin-based structures involved in macrophage fusion, i.e., podosomes, zipper-like structures, and tunneling nanotubes (TNT). Finally, the localization and potential role of the key fusion mediators related to the formation of these F-actin structures will be discussed. This review intends to present the current status of knowledge of the molecular and cellular mechanisms supporting multinucleation of myeloid cells, highlighting the gaps still existing, and contributing to the proposition of potential disease-specific MGC markers and/or therapeutic targets.

scholarly journals Adipoclast: a multinucleated fat-eating macrophage

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antoni Olona ◽  
Subhankar Mukhopadhyay ◽  
Charlotte Hateley ◽  
Fernando O. Martinez ◽  
Siamon Gordon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasma Membrane ◽  
Cell Membrane ◽  
Cell Fusion ◽  
Metabolic Activity ◽  
Current Knowledge ◽  
Giant Cells ◽  
Multinucleated Giant Cells ◽  
Review Current

AbstractCell membrane fusion and multinucleation in macrophages are associated with physiologic homeostasis as well as disease. Osteoclasts are multinucleated macrophages that resorb bone through increased metabolic activity resulting from cell fusion. Fusion of macrophages also generates multinucleated giant cells (MGCs) in white adipose tissue (WAT) of obese individuals. For years, our knowledge of MGCs in WAT has been limited to their description as part of crown-like structures (CLS) surrounding damaged adipocytes. However, recent evidence indicates that these cells can phagocytose oversized lipid remnants, suggesting that, as in osteoclasts, cell fusion and multinucleation are required for specialized catabolic functions. We thus reason that WAT MGCs can be viewed as functionally analogous to osteoclasts and refer to them in this article as adipoclasts. We first review current knowledge on adipoclasts and their described functions. In view of recent advances in single cell genomics, we describe WAT macrophages from a ‘fusion perspective’ and speculate on the ontogeny of adipoclasts. Specifically, we highlight the role of CD9 and TREM2, two plasma membrane markers of lipid-associated macrophages in WAT, which have been previously described as regulators of fusion and multinucleation in osteoclasts and MGCs. Finally, we consider whether strategies aiming to target WAT macrophages can be more selectively directed against adipoclasts.

Genetic Analysis of the Drosophila αPS2 Integrin Subunit Reveals Discrete Adhesive, Morphogenetic and Sarcomeric Functions

Genetics ◽  
1998 ◽  
Vol 148 (3) ◽  
pp. 1127-1142 ◽  
Author(s):  
James W Bloor ◽  
Nicholas H Brown
Keyword(s):  
Genetic Analysis ◽  
Good Evidence ◽  
Integrin Subunit ◽  
Surface Receptors ◽  
Intracellular Signals ◽  
Cell Substrate ◽  
Interallelic Complementation ◽  
Cell To Cell Adhesion ◽  
Integrin Family

AbstractThe integrin family of cell surface receptors mediates cell-substrate and cell-to-cell adhesion and transmits intracellular signals. In Drosophila there is good evidence for an adhesive role of integrins, but evidence for integrin signalling has remained elusive. Each integrin is an αβ heterodimer, and the Drosophila βPS subunit forms at least two integrins by association with different α subunits: αPS1βPS (PS1) and αPS2βPS (PS2). The complex pattern of PS2 integrin expression includes, but is more extensive than, the sites where PS2 has a known requirement. In order to investigate whether PS2 integrin is required at these additional sites and/or has functions besides mediating adhesion, a comprehensive genetic analysis of inflated, the gene that encodes αPS2, was performed. We isolated 35 new inflated alleles, and obtained 10 alleles from our colleagues. The majority of alleles are amorphs (36/45) or hypomorphs (4/45), but five alleles that affect specific developmental processes were identified. Interallelic complementation between these alleles suggests that some may affect distinct functional domains of the αPS2 protein, which specify particular interactions that promote adhesion or signalling. One new allele reveals that the PS2 integrin is required for the development of the adult halteres and legs as well as the wing.

scholarly journals PLCγ2 regulates TREM2 signalling and integrin-mediated adhesion and migration of human iPSC-derived macrophages

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juliane Obst ◽  
Hazel L. Hall-Roberts ◽  
Thomas B. Smith ◽  
Mira Kreuzer ◽  
Lorenza Magno ◽  
...  
Keyword(s):  
Calcium Release ◽  
Cell Function ◽  
Immune Cell ◽  
Induced Pluripotent Stem Cell ◽  
Myeloid Cell ◽  
Cellular Adhesion ◽  
Calcium Flux ◽  
Surface Receptors ◽  
And Migration

AbstractHuman genetic studies have linked rare coding variants in microglial genes, such as TREM2, and more recently PLCG2 to Alzheimer’s disease (AD) pathology. The P522R variant in PLCG2 has been shown to confer protection for AD and to result in a subtle increase in enzymatic activity. PLCγ2 is a key component of intracellular signal transduction networks and induces Ca2+ signals downstream of many myeloid cell surface receptors, including TREM2. To explore the relationship between PLCγ2 and TREM2 and the role of PLCγ2 in regulating immune cell function, we generated human induced pluripotent stem cell (iPSC)- derived macrophages from isogenic lines with homozygous PLCG2 knockout (Ko). Stimulating TREM2 signalling using a polyclonal antibody revealed a complete lack of calcium flux and IP1 accumulation in PLCγ2 Ko cells, demonstrating a non-redundant role of PLCγ2 in calcium release downstream of TREM2. Loss of PLCγ2 led to broad changes in expression of several macrophage surface markers and phenotype, including reduced phagocytic activity and survival, while LPS-induced secretion of the inflammatory cytokines TNFα and IL-6 was unaffected. We identified additional deficits in PLCγ2- deficient cells that compromised cellular adhesion and migration. Thus, PLCγ2 is key in enabling divergent cellular functions and might be a promising target to increase beneficial microglial functions.

scholarly journals DC-STAMP is essential for cell–cell fusion in osteoclasts and foreign body giant cells

2005 ◽  
Vol 202 (3) ◽  
pp. 345-351 ◽  
Author(s):  
Mitsuru Yagi ◽  
Takeshi Miyamoto ◽  
Yumi Sawatani ◽  
Katsuya Iwamoto ◽  
Naobumi Hosogane ◽  
...  
Keyword(s):  
Foreign Body ◽  
Cell Fusion ◽  
Transmembrane Protein ◽  
Cell Formation ◽  
Giant Cells ◽  
Foreign Body Giant Cell ◽  
Bone Homeostasis ◽  
Macrophage Cell ◽  
Giant Cell Formation ◽  
Deficient Mice

Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell–specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP–deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP–deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

Psychological Resilience Provides No Independent Protection From Suicidal Risk

Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey
Keyword(s):  
Risk Factors ◽  
Well Being ◽  
Current Status ◽  
Psychological Resilience ◽  
Cross Sectional ◽  
Life Project ◽  
Resilience Factors ◽  
First Time

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.

INTERPRETATION OF SINO-RUSSIAN CULTURE AND HUMANITIES COOPERATION IN THE NEW ERA

2020 ◽  
Vol 10 (3) ◽  
pp. 186-193
Author(s):  
REN YANYAN ◽  
Keyword(s):  
Current Status ◽  
Human Relations ◽  
New Era ◽  
Russian Culture ◽  
The People ◽  
Starting Point ◽  
Cooperative Partnership ◽  
Belt And Road ◽  
The Belt And Road

The friendship between nations lies in the mutual affinity of the people, and the people’s affinity lies in the communion of hearts. The cultural and humanities cooperation between China and Russia has a long history. In recent years, under the role of the“Belt and Road” initiative, the SCO, and the Sino-Russian Humanities Cooperation Committee, Sino-Russian culture and humanities cooperation has continued to deepen. Entering a new era, taking the opportunity to promote Sino-Russian relations into a “new era China-Russia comprehensive strategic cooperative partnership”, the development of human relations between the two countries has entered a new historical starting point, while also facing a series of problems and challenges. This article is based on the current status of Sino-Russian human relations in the new era, interprets the characteristics of Sino-Russian human relations in the new era, analyzes the problems and challenges of Sino-Russian human relations in the new era, and tries to propose solutions and solutions with a view to further developing Sino-Russian cultural and humanities relations in the new era. It is a useful reference, and provides a reference for future related research, and ultimately helps the Sino-Russian cultural and humanities relations in the new era to be stable and far-reaching.

Role of Pharmacogenomics in Antiepileptic Drug Therapy: Current Status and Future Perspectives

2018 ◽  
Vol 23 (37) ◽  
pp. 5760-5765 ◽  
Author(s):  
Antonio Gambardella ◽  
Angelo Labate ◽  
Laura Mumoli ◽  
Iscia Lopes-Cendes ◽  
Fernando Cendes
Keyword(s):  
Drug Therapy ◽  
Antiepileptic Drug ◽  
Current Status ◽  
Future Perspectives ◽  
Antiepileptic Drug Therapy

mTORC and PKCε in Regulation of Alcohol Use Disorder

2020 ◽  
Vol 20 (17) ◽  
pp. 1696-1708 ◽  
Author(s):  
Athirah Hanim ◽  
Isa Naina Mohamed ◽  
Rashidi M. Pakri Mohamed ◽  
Srijit Das ◽  
Norefrina Shafinaz Md Nor ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Alcohol Intake ◽  
Potential Role ◽  
Synaptic Proteins ◽  
Cellular Mechanisms ◽  
Kinase C ◽  
Protein Kinase C Epsilon ◽  
Seeking Behavior

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.

scholarly journals Membrane condenser as emerging technology for water recovery and gas pre-treatment: current status and perspectives

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Adele Brunetti ◽  
Francesca Macedonio ◽  
Giuseppe Barbieri ◽  
Enrico Drioli
Keyword(s):  
Current Status ◽  
Innovative Technology ◽  
Water Recovery ◽  
Treatment Unit ◽  
Treatment Stage ◽  
Treatment Technologies ◽  
Pre Treatment ◽  
And Control

Abstract The recent roadmap of SPIRE initiative includes the development of “new separation, extraction and pre-treatment technologies” as one of the “key actions” for boosting sustainability, enhancing the availability and quality of existing resources. Membrane condenser is an innovative technology that was recently investigated for the recovery of water vapor for waste gaseous streams, such as flue gas, biogas, cooling tower plumes, etc. Recently, it has been also proposed as pre-treatment unit for the reduction and control of contaminants in waste gaseous streams (SOx and NOx, VOCs, H2S, NH3, siloxanes, halides, particulates, organic pollutants). This perspective article reports recent progresses in the applications of the membrane condenser in the treatment of various gaseous streams for water recovery and contaminant control. After an overview of the operating principle, the membranes used, and the main results achieved, the work also proposes the role of this technology as pre-treatment stage to other separation technologies. The potentialities of the technology are also discussed aspiring to pave the way towards the development of an innovative technology where membrane condenser can cover a key role in redesigning the whole upgrading process.

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