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Journal of Plant Physiology Nov 2021Cold stress is one of the harsh environmental stresses that adversely affect plant growth and crop yields in the Qinghai-Tibet Plateau. However, plants have evolved... (Review)
Review
Cold stress is one of the harsh environmental stresses that adversely affect plant growth and crop yields in the Qinghai-Tibet Plateau. However, plants have evolved mechanisms to overcome the impact of cold stress. Progress has been made in understanding how plants perceive and transduce low-temperature signals to tolerate cold stress. Small signaling molecules are crucial for cellular signal transduction by initiating the downstream signaling cascade that helps plants to respond to cold stress. These small signaling molecules include calcium, reactive oxygen species, nitric oxide, hydrogen sulfide, cyclic guanosine monophosphate, phosphatidic acid, and sphingolipids. The small signaling molecules are involved in many aspects of cellular and physiological functions, such as inducing gene expression and activating hormone signaling, resulting in upregulation of the antioxidant enzyme activities, osmoprotectant accumulation, malondialdehyde reduction, and photosynthesis improvement. We summarize our current understanding of the roles of the small signaling molecules in cold stress in plants, and highlight their crosstalk in cold signaling transduction. These discoveries help us understand how the plateau plants adapt to the severe alpine environment as well as to develop new crops tolerating cold stress in the Qinghai-Tibet Plateau.
Topics: Adaptation, Physiological; Antioxidants; Calcium; Cold Temperature; Cold-Shock Response; Crops, Agricultural; Cyclic GMP; Hydrogen Sulfide; Nitric Oxide; Phosphatidic Acids; Plant Physiological Phenomena; Plants; Reactive Oxygen Species; Signal Transduction; Sphingolipids; Stress, Physiological
PubMed: 34601338
DOI: 10.1016/j.jplph.2021.153534 -
Biomolecules Apr 2018Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural... (Review)
Review
Cellular membranes are composed of thousands of different lipids usually maintained within a narrow range of concentrations. In addition to their well-known structural and metabolic roles, signaling functions for many lipids have also emerged over the last two decades. The latter largely depend on the ability of particular classes of lipids to interact specifically with a great variety of proteins and to regulate their localization and activity. Among these lipids, phosphatidic acid (PA) plays a unique role in a large repertoire of cellular activities, most likely in relation to its unique biophysical properties. However, until recently, only incomplete information was available to model the interaction between PA and its protein partners. The development of new liposome-based assays as well as molecular dynamic simulation are now providing novel information. We will review the different factors that have shown to modulate the capacity of PA to interact with specific domains in target proteins.
Topics: Animals; Cell Membrane; Humans; Phosphatidic Acids; Phospholipase D; Protein Binding; Static Electricity
PubMed: 29690573
DOI: 10.3390/biom8020020 -
Cells Dec 2021The need to gain insights into the molecular details of peripheral membrane proteins' specificity towards phosphatidic acid (PA) is undeniable. The variety of PA species...
The need to gain insights into the molecular details of peripheral membrane proteins' specificity towards phosphatidic acid (PA) is undeniable. The variety of PA species classified in terms of acyl chain length and saturation translates into a complicated, enigmatic network of functional effects that exert a critical influence on cell physiology. As a consequence, numerous studies on the importance of phosphatidic acid in human diseases have been conducted in recent years. One of the key proteins in this context is mTOR, considered to be the most important cellular sensor of essential nutrients while regulating cell proliferation, and which also appears to require PA to build stable and active complexes. Here, we investigated the specific recognition of three physiologically important PA species by the mTOR FRB domain in the presence or absence of cholesterol in targeted membranes. Using a broad range of methods based on model lipid membrane systems, we elucidated how the length and saturation of PA acyl chains influence specific binding of the mTOR FRB domain to the membrane. We also discovered that cholesterol exerts a strong modulatory effect on PA-FRB recognition. Our data provide insight into the molecular details of some physiological effects reported previously and reveal novel mechanisms of fine-tuning the signaling cascades dependent on PA.
Topics: Cholesterol; Humans; Phosphatidic Acids; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 35011681
DOI: 10.3390/cells11010119 -
Biochemical and Biophysical Research... May 2020Diacylglycerol kinase (DGK) α enhances the proliferation of melanoma and hepatocellular carcinoma cells whereas, in contrast, DGKα induces a nonproliferative state in...
Diacylglycerol kinase (DGK) α enhances the proliferation of melanoma and hepatocellular carcinoma cells whereas, in contrast, DGKα induces a nonproliferative state in T cells. We previously found that DGKα produces palmitic acid (16:0)-containing PA species, such as 16:0/16:0- and 16:0/18:0-PA, in melanoma cells under serum-starved (nonproliferative) conditions. In the present study, we identified the PA species generated by DGKα in T cells under serum-starved (nonproliferative) conditions. We found that serum starvation markedly increased the levels of many PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:1/18:2-, 16:1/18:1-, 16:0/18:1-, 16:0/18:0-, 18:1/18:2-, 18:1/18:1- and 18:0/18:1-PA, in Jurkat T cells. In lysates from serum-starved Jurkat T cells, DGKα activity, which was Ca-dependent and sensitive to a DGKα-specific inhibitor (CU-3), was substantially increased, indicating its activation. Moreover, CU-3 (1-10 μM) significantly reduced the amounts of palmitic acid- and/or palmitoleic acid (16:1)-containing PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:0/18:1- and 16:0/18:0-PA, which were increased by serum starvation. These results indicate that DGKα generates different PA species in starved melanoma cells (palmitic acid-containing PA species) and T cells (palmitic acid- and/or palmitoleic acid (16:1)-containing PA species). Therefore, the differences in the PA molecular species may account for the opposing functions of DGKα in melanoma and T cells.
Topics: Calcium; Cell Proliferation; Chromatography, Liquid; Diacylglycerol Kinase; Fatty Acids, Monounsaturated; Humans; Jurkat Cells; Melanoma; Palmitic Acid; Phosphatidic Acids; Rhodanine; Sulfonamides; T-Lymphocytes; Tandem Mass Spectrometry
PubMed: 32184022
DOI: 10.1016/j.bbrc.2020.02.162 -
Biochemical Society Transactions Feb 2016Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] requires replenishment from a... (Review)
Review
Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] requires replenishment from a larger pool of phosphatidylinositol (PtdIns) via sequential phosphorylation by PtdIns 4-kinases and phosphatidylinositol 4-phosphate (PtdIns4P) 5-kinases. Since PtdIns is synthesized in the endoplasmic reticulum (ER) and PtdIns(4,5)P2 is generated in the PM, it has been postulated that PtdIns transfer proteins (PITPs) provide the means for this lipid transfer function. Recent studies identified the large PITP protein, Nir2 as important for PtdIns transfer from the ER to the PM. It was also found that Nir2 was required for the transfer of phosphatidic acid (PtdOH) from the PM to the ER. In Nir2-depleted cells, activation of PLC leads to PtdOH accumulation in the PM and PtdIns synthesis becomes severely impaired. In quiescent cells, Nir2 is localized to the ER via interaction of its FFAT domain with ER-bound VAMP-associated proteins VAP-A and-B. After PLC activation, Nir2 also binds to the PM via interaction of its C-terminal domains with diacylglycerol (DAG) and PtdOH. Through these interactions, Nir2 functions in ER-PM contact zones. Mutations in VAP-B that have been identified in familial forms of amyotrophic lateral sclerosis (ALS or Lou-Gehrig's disease) cause aggregation of the VAP-B protein, which then impairs its binding to several proteins, including Nir2. These findings have shed new lights on the importance of non-vesicular lipid transfer of PtdIns and PtdOH in ER-PM contact zones with a possible link to a devastating human disease.
Topics: Animals; Biological Transport; Calcium-Binding Proteins; Cell Membrane; Endoplasmic Reticulum; Humans; Phosphatidic Acids; Phosphatidylinositols; Type C Phospholipases
PubMed: 26862206
DOI: 10.1042/BST20150187 -
Progress in Lipid Research Jul 2018Phosphatidic acid (PA) is a simple phospholipid observed in most organisms. PA acts as a key metabolic intermediate and a second messenger that regulates many cell... (Review)
Review
Phosphatidic acid (PA) is a simple phospholipid observed in most organisms. PA acts as a key metabolic intermediate and a second messenger that regulates many cell activities. In plants, PA is involved in numerous cell responses induced by hormones, stress inputs and developmental processes. Interestingly, PA production can be triggered by opposite stressors, such as cold and heat, or by hormones that are considered to be antagonistic, such as abscisic acid and salicylic acid. This property questions the specificity of the responses controlled by PA. Are there generic responses to PA, meaning that cell regulation triggered by PA would be always the same, even in opposite physiological situations? Alternatively, do the responses to PA differ according to the physiological context within the cells? If so, the mechanisms that regulate the divergence of PA-controlled reactions are poorly defined. This review summarizes the latest opinions on how PA signalling is directed in plant cells and examines the intrinsic properties of PA that enable its regulatory diversity. We propose a concept whereby PA regulatory messages are perceived as complex "signatures" that take into account their production site, the availability of target proteins and the relevant cellular environments.
Topics: Amino Acid Sequence; Binding Sites; Molecular Structure; Phosphatidic Acids; Plant Physiological Phenomena; Plant Proteins; Plants; Protein Binding; Signal Transduction
PubMed: 29842906
DOI: 10.1016/j.plipres.2018.05.003 -
Lipids Mar 2023Cancer cells are known to survive in a hypoxic microenvironment by altering their lipid metabolism as well as their energy metabolism. In this study, Caco-2 cells...
Cancer cells are known to survive in a hypoxic microenvironment by altering their lipid metabolism as well as their energy metabolism. In this study, Caco-2 cells derived from human colon cancer, were found to have elevated intracellular levels of phosphatidic acid and its lysoform, lysophosphatidic acid (LPA), under hypoxic conditions. Our results suggested that the elevation of LPA in Caco-2 cells was mainly due to the combined increases in cellular levels of lysophosphatidylcholine and lysophosphatidylethanolamine by phospholipase A and subsequent hydrolysis to LPA by lysophospholipase D. We detected the Ca -stimulated choline-producing activities toward exogenous lysophosphatidylcholines in whole Caco-2 cell homogenates, indicating their involvement in the LPA production in intact Caco-2 cells.
Topics: Humans; Phosphatidic Acids; Caco-2 Cells; Lysophospholipids; Lysophosphatidylcholines
PubMed: 36708255
DOI: 10.1002/lipd.12366 -
Astrocytic Neuroimmunological Roles Interacting with Microglial Cells in Neurodegenerative Diseases.International Journal of Molecular... Jan 2023Both astrocytic and microglial functions have been extensively investigated in healthy subjects and neurodegenerative diseases. For astrocytes, not only various... (Review)
Review
Both astrocytic and microglial functions have been extensively investigated in healthy subjects and neurodegenerative diseases. For astrocytes, not only various sub-types were identified but phagocytic activity was also clarified recently and is making dramatic progress. In this review paper, we mostly focus on the functional role of astrocytes in the extracellular matrix and on interactions between reactive astrocytes and reactive microglia in normal states and in neurodegenerative diseases, because the authors feel it is necessary to elucidate the mechanisms among activated glial cells in the pathology of neurological diseases in order to pave the way for drug discovery. Finally, we will review cyclic phosphatidic acid (cPA), a naturally occurring phospholipid mediator that induces a variety of biological activities in the brain both in vivo and in vitro. We propose that cPA may serve as a novel therapeutic molecule for the treatment of brain injury and neuroinflammation.
Topics: Humans; Microglia; Astrocytes; Neurodegenerative Diseases; Central Nervous System; Neuroglia; Phosphatidic Acids
PubMed: 36675113
DOI: 10.3390/ijms24021599 -
The Journal of Biological Chemistry Feb 2020PlsX is the first enzyme in the pathway that produces phosphatidic acid in Gram-positive bacteria. It makes acylphosphate from acyl-acyl carrier protein (acyl-ACP) and...
PlsX is the first enzyme in the pathway that produces phosphatidic acid in Gram-positive bacteria. It makes acylphosphate from acyl-acyl carrier protein (acyl-ACP) and is also involved in coordinating phospholipid and fatty acid biosyntheses. PlsX is a peripheral membrane enzyme in but how it associates with the membrane remains largely unknown. In the present study, using fluorescence microscopy, liposome sedimentation, differential scanning calorimetry, and acyltransferase assays, we determined that PlsX binds directly to lipid bilayers and identified its membrane anchoring moiety, consisting of a hydrophobic loop located at the tip of two amphipathic dimerization helices. To establish the role of the membrane association of PlsX in acylphosphate synthesis and in the flux through the phosphatidic acid pathway, we then created mutations and gene fusions that prevent PlsX's interaction with the membrane. Interestingly, phospholipid synthesis was severely hampered in cells in which PlsX was detached from the membrane, and results from metabolic labeling indicated that these cells accumulated free fatty acids. Because the same mutations did not affect PlsX transacylase activity, we conclude that membrane association is required for the proper delivery of PlsX's product to PlsY, the next enzyme in the phosphatidic acid pathway. We conclude that PlsX plays a dual role in phospholipid synthesis, acting both as a catalyst and as a chaperone protein that mediates substrate channeling into the pathway.
Topics: Bacillus subtilis; Bacterial Proteins; Catalysis; Escherichia coli; Fatty Acids; Lipogenesis; Metabolic Networks and Pathways; Phosphatidic Acids; Phospholipids
PubMed: 31919098
DOI: 10.1074/jbc.RA119.011147 -
Journal of Biochemistry May 2022The transfer of phospholipids from the endoplasmic reticulum (ER) to mitochondria via the mitochondria-ER contact site (MERCS) is essential for maintaining mitochondrial...
The transfer of phospholipids from the endoplasmic reticulum (ER) to mitochondria via the mitochondria-ER contact site (MERCS) is essential for maintaining mitochondrial function and integrity. Here, we identified RMDN3/PTPIP51, possessing phosphatidic acid (PA)-transfer activity, as a neighbouring protein of the mitochondrial E3 ubiquitin ligase MITOL/MARCH5 by proximity-dependent biotin labelling using APEX2. We found that MITOL interacts with and ubiquitinates RMDN3. Mutational analysis identified lysine residue 89 in RMDN3 as a site of ubiquitination by MITOL. Loss of MITOL or the substitution of lysine 89 to arginine in RMDN3 significantly reduced the PA-binding activity of RMDN3, suggesting that MITOL regulates the transport of PA to mitochondria by activating RMDN3. Our findings imply that ubiquitin signalling regulates phospholipid transport at the MERCS.
Topics: Endoplasmic Reticulum; Lysine; Membrane Proteins; Mitochondrial Proteins; Phosphatidic Acids; Ubiquitin-Protein Ligases
PubMed: 34964862
DOI: 10.1093/jb/mvab153