scholarly journals Examining the Underappreciated Role of S-Acylated Proteins as Critical Regulators of Phagocytosis and Phagosome Maturation in Macrophages

2021 ◽  
Vol 12 ◽  
Author(s):  
Charneal L. Dixon ◽  
Katrina Mekhail ◽  
Gregory D. Fairn
Keyword(s):  
Signal Transduction ◽  
Fatty Acids ◽  
Sulfur Atom ◽  
Cysteine Residue ◽  
Apoptotic Cells ◽  
Membrane Remodeling ◽  
Phagosome Maturation ◽  
Thioester Bond ◽  
Acylated Proteins

Phagocytosis is a receptor-mediated process used by cells to engulf a wide variety of particulates, including microorganisms and apoptotic cells. Many of the proteins involved in this highly orchestrated process are post-translationally modified with lipids as a means of regulating signal transduction, membrane remodeling, phagosome maturation and other immunomodulatory functions of phagocytes. S-acylation, generally referred to as S-palmitoylation, is the post-translational attachment of fatty acids to a cysteine residue exposed topologically to the cytosol. This modification is reversible due to the intrinsically labile thioester bond between the lipid and sulfur atom of cysteine, and thus lends itself to a variety of regulatory scenarios. Here we present an overview of a growing number of S-acylated proteins known to regulate phagocytosis and phagosome biology in macrophages.

scholarly journals Autophagosomes fuse to phagosomes and play important roles in the degradation of apoptotic cells in Caenorhabditis elegans

2021 ◽  
Author(s):  
Omar Pena-Ramos ◽  
Lucia Chiao ◽  
Xianghua Liu ◽  
Tianyou Yao ◽  
Henry He ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Small Gtpase ◽  
Apoptotic Cells ◽  
Phagosome Maturation ◽  
Double Membrane ◽  
C Elegans ◽  
Intracellular Organelles ◽  
Intracellular Vesicles ◽  
Cellular Components

Autophagosomes are double-membrane intracellular vesicles that degrade protein aggregates, intracellular organelles, and other cellular components. In the nematode Caenorhabditis elegans, 113 somatic cells undergo apoptosis during embryogenesis and are engulfed and degraded by their neighboring cells. We discovered a novel role of autophagosomes in facilitating the degradation of apoptotic cells in C. elegans embryos using a real-time imaging technique. Specifically, double-membrane autophagosomes in engulfing cells are recruited to the surfaces of phagosomes containing apoptotic cells and subsequently fuse to phagosomes, allowing the inner membrane to enter the phagosomal lumen. Mutants defective in the production of autophagosomes display significant delays in the degradation of apoptotic cells, demonstrating the important contribution of autophagosomes to this process. The signaling pathway led by the phagocytic receptor CED-1, CED-1s adaptor CED-6, and the large GTPase dynamin (DYN-1) promote the recruitment of autophagosomes to phagosomes. Moreover, the subsequent fusion of autophagosomes with phagosomes requires the functions of the small GTPase RAB-7 and the HOPS complex. Our findings reveal that, unlike the single-membrane, LC3- associated phagocytosis (LAP) vesicles reported for mammalian phagocytes, canonical autophagosomes function in the clearance of C. elegans apoptotic cells. These findings add autophagosomes to the collection of intracellular organelles that contribute to phagosome maturation, identify novel crosstalk between the autophagy and phagosome maturation pathways, and discover the upstream factors that initiate this crosstalk.

scholarly journals Modification of Glyceraldehyde-3-Phosphate Dehydrogenase with Nitric Oxide: Role in Signal Transduction and Development of Apoptosis

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1656
Author(s):  
Vladimir I. Muronetz ◽  
Maria V. Medvedeva ◽  
Irina A. Sevostyanova ◽  
Elena V. Schmalhausen
Keyword(s):  
Nitric Oxide ◽  
Signal Transduction ◽  
Cysteine Residue ◽  
Nuclear Proteins ◽  
Passive Transport ◽  
Carrier Proteins ◽  
Catalytic Cysteine ◽  
Induction Of Apoptosis ◽  
Direct Confirmation

This review focuses on the consequences of GAPDH S-nitrosylation at the catalytic cysteine residue. The widespread hypothesis according to which S-nitrosylation causes a change in GAPDH structure and its subsequent binding to the Siah1 protein is considered in detail. It is assumed that the GAPDH complex with Siah1 is transported to the nucleus by carrier proteins, interacts with nuclear proteins, and induces apoptosis. However, there are several conflicting and unproven elements in this hypothesis. In particular, there is no direct confirmation of the interaction between the tetrameric GAPDH and Siah1 caused by S-nitrosylation of GAPDH. The question remains as to whether the translocation of GAPDH into the nucleus is caused by S-nitrosylation or by some other modification of the catalytic cysteine residue. The hypothesis of the induction of apoptosis by oxidation of GAPDH is considered. This oxidation leads to a release of the coenzyme NAD+ from the active center of GAPDH, followed by the dissociation of the tetramer into subunits, which move to the nucleus due to passive transport and induce apoptosis. In conclusion, the main tasks are summarized, the solutions to which will make it possible to more definitively establish the role of nitric oxide in the induction of apoptosis.

Alcohol intake impairs glucose counterregulation during acute insulin-induced hypoglycemia in IDDM patients. Evidence for a critical role of free fatty acids

Diabetes ◽  
1993 ◽  
Vol 42 (11) ◽  
pp. 1626-1634 ◽  
Author(s):  
A. Avogaro ◽  
P. Beltramello ◽  
L. Gnudi ◽  
A. Maran ◽  
A. Valerio ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Alcohol Intake ◽  
Critical Role

scholarly journals cROStalk for Life: Uncovering ROS Signaling in Plants and Animal Systems, from Gametogenesis to Early Embryonic Development

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 525
Author(s):  
Valentina Lodde ◽  
Piero Morandini ◽  
Alex Costa ◽  
Irene Murgia ◽  
Ignacio Ezquer
Keyword(s):  
Signal Transduction ◽  
Signaling Pathways ◽  
Analytical Techniques ◽  
Antioxidant Systems ◽  
Developmental Studies ◽  
Science Field ◽  
Ros Signaling ◽  
Reproductive Processes

This review explores the role of reactive oxygen species (ROS)/Ca2+ in communication within reproductive structures in plants and animals. Many concepts have been described during the last years regarding how biosynthesis, generation products, antioxidant systems, and signal transduction involve ROS signaling, as well as its possible link with developmental processes and response to biotic and abiotic stresses. In this review, we first addressed classic key concepts in ROS and Ca2+ signaling in plants, both at the subcellular, cellular, and organ level. In the plant science field, during the last decades, new techniques have facilitated the in vivo monitoring of ROS signaling cascades. We will describe these powerful techniques in plants and compare them to those existing in animals. Development of new analytical techniques will facilitate the understanding of ROS signaling and their signal transduction pathways in plants and mammals. Many among those signaling pathways already have been studied in animals; therefore, a specific effort should be made to integrate this knowledge into plant biology. We here discuss examples of how changes in the ROS and Ca2+ signaling pathways can affect differentiation processes in plants, focusing specifically on reproductive processes where the ROS and Ca2+ signaling pathways influence the gametophyte functioning, sexual reproduction, and embryo formation in plants and animals. The study field regarding the role of ROS and Ca2+ in signal transduction is evolving continuously, which is why we reviewed the recent literature and propose here the potential targets affecting ROS in reproductive processes. We discuss the opportunities to integrate comparative developmental studies and experimental approaches into studies on the role of ROS/ Ca2+ in both plant and animal developmental biology studies, to further elucidate these crucial signaling pathways.

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