• Journal of Marine Life Science
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• v.5 no.2
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• pp.92-98
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• 2020

Heat shock proteins (HSPs) are highly conserved cellular proteins that contribute to adaptive responses of organisms to a variety of stressors. In response to stressors, cellular levels of HSPs are increased and play critical roles in protein stability, folding and molecular trafficking. The mRNA expression pattern of two well-known heat shock protein transcripts, HSP70 and HSP90 were studied in two tissues of nerve ganglia, cerebral ganglion and pleuropedal ganglion of Pacific abalone (Haliotis discus hannai). It was observed that both HSP70 and HSP90 transcripts were upregulated under heat stress in both ganglion tissues. Expression level of HSP70 was found higher than HSP90 in both ganglia whereas cerebral ganglion showed higher expression than pleuropedal ganglion. The HSP70 and HSP90 showed higher expression at Day-1 after exposed to heat stress, later decreased at Day-3 and Day-7 onwards. The present result suggested that HSP70 and HSP90 synthesize in nerve ganglion tissues and may provide efficient protection from stress.

• BMB Reports
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• v.56 no.11
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• pp.575-583
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• 2023

Mitochondria, fundamental cellular organelles that govern energy metabolism, hold a pivotal role in cellular vitality. While consuming dioxygen to produce adenosine triphosphate (ATP), the electron transfer process within mitochondria can engender the formation of reactive oxygen species that exert dual roles in endothelial homeostatic signaling and oxidative stress. In the context of the intricate electron transfer process, several metal ions that include copper, iron, zinc, and manganese serve as crucial cofactors in mitochondrial metalloenzymes to mediate the synthesis of ATP and antioxidant defense. In this mini review, we provide a comprehensive understanding of the coordination chemistry of mitochondrial cuproenzymes. In detail, cytochrome c oxidase (CcO) reduces dioxygen to water coupled with proton pumping to generate an electrochemical gradient, while superoxide dismutase 1 (SOD1) functions in detoxifying superoxide into hydrogen peroxide. With an emphasis on the catalytic reactions of the copper metalloenzymes and insights into their ligand environment, we also outline the metalation process of these enzymes throughout the copper trafficking system. The impairment of copper homeostasis can trigger mitochondrial dysfunction, and potentially lead to the development of copper-related disorders. We describe the current knowledge regarding copper-mediated toxicity mechanisms, thereby shedding light on prospective therapeutic strategies for pathologies intertwined with copper dyshomeostasis.

• Analytical Science and Technology
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• v.28 no.1
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• pp.65-71
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• 2015

Intracellular organelles in eukaryotic cells play important roles in many cellular functions. Intracellular trafficking of many proteins to specific intracellular organelles is tightly regulated by various mechanisms in cells. Therefore, elucidating the targeting mechanism of novel markers for intracellular organelles is important for cellular physiology and pathology. In this study, we tried to identify the peptides which could bind to specific glycolipid in cellular membrane using GFP-fused glycolipid-binding peptides, and analyzed their cellular localization. As a result, we could identify mitochondria-, Golgi- or plasma membrane-targeting peptides. Furthermore, we found that the plasma membrane-targeting peptide was localized to the plasma membrane via electrostatic interactions. Thus, our results suggest that various glycolipid-binding peptides could be used as intracellular organelles markers.

• BMB Reports
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• v.42 no.6
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• pp.324-330
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• 2009

Autophagy is a bulk lysosomal degradation process important in development, differentiation and cellular homeostasis in multiple organs. Interestingly, neuronal survival is highly dependent on autophagy due to its post-mitotic nature, polarized morphology and active protein trafficking. A growing body of evidence now suggests that alteration or dysfunction of autophagy causes accumulation of abnormal proteins and/or damaged organelles, thereby leading to neurodegenerative disease. Although autophagy generally prevents neuronal cell death, it plays a protective or detrimental role in neurodegenerative disease depending on the environment. In this review, the two sides of autophagy will be discussed in the context of several neurodegenerative diseases.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.109-114
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• 2016

In Drosophila, rhomboid proteases are active cardinal regulators of epidermal growth factor receptor (EGFR) signaling pathway. iRhom1 and iRhom2, which are inactive homologs of rhomboid intramembrane serine proteases, are lacking essential catalytic residues. These are necessary for maturation and trafficking of tumor necrosis factor-alpha (TNF-${\alpha}$) converting enzyme (TACE) from endoplasmic reticulum (ER) to plasma membrane through Golgi, and associated with the fates of various ligands for EGFR. Recent studies have clarified that the activation or downregulation of EGFR signaling pathways by alteration of iRhoms are connected to several human diseases including tylosis with esophageal cancer (TOC) which is the autosomal dominant syndrom, breast cancer, and Alzheimer's disease. Thus, this review focuses on our understanding of iRhoms and the involved mechanisms in the cellular processes.

• Molecules and Cells
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• v.28 no.1
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• pp.1-5
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• 2009

Vascular endothelial growth factor (VEGF) is essential for many angiogenic processes both in normal and pathological conditions. However, the signaling pathways involved in VEGF-induced angiogenesis are incompletely understood. The protein kinase D1 (PKD1), a newly described calcium/calmodulin-dependent serine/threonine kinase, has been implicated in cell migration, proliferation and membrane trafficking. Increasing evidence suggests critical roles for PKD1-mediated signaling pathways in endothelial cells, particularly in the regulation of VEGF-induced angiogenesis. Recent studies show that class IIa histone deacetylases (HDACs) are PKD1 substrates and VEGF signal-responsive repressors of myocyte enhancer factor-2 (MEF2) transcriptional activation in endothelial cells. This review provides a guide to PKD1 signaling pathways and the direct downstream targets of PKD1 in VEGF signaling, and suggests important functions of PKD1 in angiogenesis.

• BMB Reports
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• v.53 no.1
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• pp.28-34
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• 2020

Sphingolipids are ubiquitous building blocks of eukaryotic cell membranes that function as signaling molecules for regulating a diverse range of cellular processes, including cell proliferation, growth, survival, immune-cell trafficking, vascular and epithelial integrity, and inflammation. Recently, several studies have highlighted the pivotal role of sphingolipids in neuroinflammatory regulation. Sphingolipids have multiple functions, including induction of the expression of various inflammatory mediators and regulation of neuroinflammation by directly effecting the cells of the central nervous system. Accumulating evidence points to sphingolipid engagement in neuroinflammatory disorders, including Alzheimer's and Parkinson's diseases. Abnormal sphingolipid alterations, which involves an increase in ceramide and a decrease in sphingosine kinase, are observed during neuroinflammatory disease. These trends are observed early during disease development, and thus highlight the potential of sphingolipids as a new therapeutic and diagnostic target for neuroinflammatory diseases.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.1
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• pp.312-317
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• 2011

Vanilloid receptor TRPV1 (known as capsaicin channel, transient receptor potential vanilloid 1) is known to be a key protein in the pain signal transduction. However, the proteins controlling the activity of the channel are not much known yet. Recently mouse Rab11-FIP3 (Rab11-family interaction protein 3) was found and reported to interact with rat TRPV1. Rab11 has been shown to play a key role in a variety of cellular processes including plasma membrane recycling, phagocytosis, and transport of secretory proteins from the trans-Golgi network. Therefore, Rab11-FIP3 was proposed to be involved in the membrane trafficking of TRPV1. In this study, the unreported rat Rab11-FIP3 was yet cloned in order to show the specific interaction of the TRPV1 and Rab11-FIP3 in the same species of rat and to examine the membrane trafficking of TRPV1. The result showed that rat Rab11-FIP3 is expected to have 489 amino acids and showed 80% identity with that of human and over 90% identity with that of mouse. Rab11-FIP3 was found to be expressed in heart, brain, kidney, testis using northern and western blot analyses. We also found that rat Rab11-FIP3 was colocalized with rat TRPV1 but not with TRPV2 of same family in the rat brain by using immunohistochemistry showing that two proteins interact specifically, suggesting the role of Rab11-FIP3 in the membrane trafficking.

• Toxicological Research
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• v.24 no.1
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• pp.1-9
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• 2008

Ptdlns(4,5)$P_2$ is a key cellular phosphoinositide that localizes in separate and distinctive pools in subcellular membrane and vesicular compartments. In membranes, Ptdlns(4,5)$P_2$ acts as a precursor to second messengers and is itself a main signaling and targeting molecule. Specific subcellular localization of type I PIP kinases directed by interacting with specific targeting module differentiates Ptdlns(4,5)$P_2$ production in a spatial and temporal manner. Several lines of evidences support the idea that Ptdlns(4,5)$P_2$ is generated in very specific pools in a spatial and temporal manner or by feeding Ptdlns(4,5)$P_2$ directly to effectors. In this concept, the interaction of PIPKI isoforms with a specific targeting module to allow precise subcellular targeting modulates highly specific Ptdlns(4,5)$P_2$ synthesis and channeling overall effectors. For instance, localization of PIPKI${\gamma}$661 to focal adhesions by an interaction with talin results in spatial and temporal production of Ptdlns(4,5)$P_2$, which regulates EGF-stimulated directional cell migration. In addition, Type $I{\gamma}$ PIPK is targeted to E-cadherin in cell adherence junction and plays a role in controlling dynamics of cell adherence junction and endocytosis of E-cadherin. Characterizing how PIP kinase isoforms are regulated by interactions with their targeting modules, as well as the mechanisms by which their product, Ptdlns(4,5)$P_2$, exerts its effects on cellular signaling processes, is crucial to understand the harmonized control of numerous cellular signaling pathways. Thus, in this review the roles of the Ptdlns(4)P(5) kinases and Ptdlns(4,5)$P_2$ were described and critically reviewed in terms of regulation of the E-cadherin trafficking, cell migration, and formation of cell adherence junction which is indispensable and is tightly controlled in epithelial-to-mesenchymal transition process.

• Molecules and Cells
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• v.46 no.4
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• pp.191-199
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• 2023

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to the insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.