Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism

Young, Barry P.; Shin, John J. H.; Orij, Rick; Chao, Jesse T.; Li, Shu‐Chen; Guan, Xue Li; Khong, Anthony; Jan, Eric; Wenk, Markus R.; Prinz, William A.; Smits, Gertien J.; Loewen, Christopher

doi:10.1126/science.1191026

Cited by 239 publications

(329 citation statements)

References 20 publications

Supporting

Mentioning

317

Contrasting

Order By: Relevance

“…This is similar to previous studies demonstrating that lipin 1 binds PA in a similar way. This suggests that perhaps the charge sensing ability of lipin 1 and 2 is a defining characteristic of the lipin family and possibly other PA-binding proteins in general (28,29). Therefore, previously unappreciated aspects of cellular physiology might be central to lipin family regulation.…”

Section: Discussionmentioning

confidence: 98%

Lipin 2 Binds Phosphatidic Acid by the Electrostatic Hydrogen Bond Switch Mechanism Independent of Phosphorylation

Eaton

Takkellapati

Lawrence

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Lipin 2 is a phosphatidic acid phosphatase (PAP) responsible for DAG formation at the ER membrane during lipogenesis. Results: A combination of biochemical approaches is used to characterize lipin 2 phosphatase activity and regulation. Conclusion: The electrostatic charge of PA regulates activity, but phosphorylation does not.Significance: These findings demonstrate differential regulation of PAP activity within the lipin family.

show abstract

Section: Discussionmentioning

confidence: 98%

Lipin 2 Binds Phosphatidic Acid by the Electrostatic Hydrogen Bond Switch Mechanism Independent of Phosphorylation

Eaton

Takkellapati

Lawrence

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…(1-4). Concomitantly, other signaling lipid molecules like phosphatidic acids (30) and lysophosphatidic acids (31) can be formed from NAPEs by NAPE-hydrolyzing phospholipase D (NAPE-PLD) (32) or through the NAPE-PLDindependent pathway (33), respectively. However, further studies are required to clarify whether endogenous PLAAT-1 produces NAPEs in the nuclear membrane of living cells and whether NAPEs play these roles on the nuclear membrane.…”

Section: Intracellular Localization Of Plaat-1lmentioning

confidence: 99%

Comparative analyses of isoforms of the calcium-independent phosphatidylethanolamine N-acyltransferase PLAAT-1 in humans and mice

Hussain

Uyama

Kawai

et al. 2016

Journal of Lipid Research

View full text Add to dashboard Cite

Fatty acyl ethanolamides [N-acylethanolamines (NAEs)] are a class of lipid mediators. Among them, arachidonoylethanolamide (anandamide) is known to be an endogenous ligand of cannabinoid receptors (namely, an endocannabinoid) (1). In addition, palmitoylethanolamide and oleoylethanolamide show biological activities such as antiinflammation, analgesia, and appetite suppression via different receptors including PPAR- (2-5). These NAEs are biosynthesized principally through a two-step pathway from membrane glycerophospholipids via N-acylphosphatidylethanolamines (NAPEs) (6). The first reaction is the transfer of an acyl chain from a glycerophospholipid molecule such as phosphatidylcholine (PC) to the amino group of phosphatidylethanolamine (PE), resulting in the formation of NAPE, and the enzyme responsible is known as PE N-acyltransferase. Very recently, cPLA 2 ɛ, a member of the cytosolic phospholipase A 2 (PLA 2 ) family (PLA2G4), has been identified as the calcium-stimulated N-acyltransferase capable of catalyzing this step (7). However, a series of our recent studies revealed that five members of the HRAS-like suppressor (HRASLS) family, which were originally discovered as tumor suppressors, possess calciumindependent phospholipid-metabolizing activities including NAPE-forming N-acyltransferase and PLA 1/2 activities (8-12), and we proposed to give HRASLS-1-5 the names phospholipase A/acyltransferase-1-5 (PLAAT-1-5), respectively (11). Among the five members, PLAAT-1 particularly received our attention because of its relatively high PE N-acyltransferase activity over PLA 1/2 activity in vitro and predominant expression in testis, skeletal muscle, brain, and heart of humans, mice, and rats, where NAPEs accumulate in response to ischemia and inflammation (11,13).Abstract N-Acylphosphatidylethanolamines (NAPEs) are a class of glycerophospholipids, which are known as precursors for different bioactive N-acylethanolamines. We previously reported that phospholipase A/acyltransferase-1 (PLAAT-1), which was originally found in mammals as a tumor suppressor, catalyzes N-acylation of phosphatidylethanolamines to form NAPEs. However, recent online database suggested the presence of an uncharacterized isoform of PLAAT-1 with an extra sequence at the N terminus. In the present study, we examined the occurrence, intracellular localization, and catalytic properties of this longer isoform, as well as the original shorter isoform from humans and mice. Our results showed that human tissues express the longer isoform but not the short isoform at all. In contrast, mice expressed both isoforms with different tissue distribution. Unlike the cytoplasmic localization of the shorter isoform, the long isoform was found in both cytoplasm and nucleus, inferring that the extra sequence harbors a nuclear localization signal. As assayed with purified proteins, neither isoform required calcium for full activity. Moreover, the overexpression of each isoform remarkably increased cellular NAPE levels. These results conclude that the new long is...

show abstract

“…A decrease in external pH can translate into a decrease in internal pH [74]. Decreased internal pH in turn was reported to suppress phospholipid metabolic genes in yeasts [75] and a lower degree of unsaturation of fatty acids in CO 2 -enriched cultures of Chlorella kessleri compared to ambient CO 2 concentrations was at least partially attributed to suppressed fatty acid synthesis and thus the promotion of desaturation of pre-existing fatty acids [76]. A higher degree of membrane lipid fatty acid saturation could be a mechanism to maintain internal pH, since a higher degree of fatty acid saturation leads to lowered fluidity and lower CO 2 -permeability of cell membranes [20].…”

Section: Fatty Acidsmentioning

confidence: 99%

Species-Specific Variations in the Nutritional Quality of Southern Ocean Phytoplankton in Response to Elevated pCO2

Wynn‐Edwards

King

Davidson

et al. 2014

Water

View full text Add to dashboard Cite

Increased seawater pCO 2 has the potential to alter phytoplankton biochemistry, which in turn may negatively affect the nutritional quality of phytoplankton as food for grazers. Our aim was to identify how Antarctic phytoplankton, Pyramimonas gelidicola, Phaeocystis antarctica, and Gymnodinium sp., respond to increased pCO 2 . Cultures were maintained in a continuous culture setup to ensure stable CO 2 concentrations. Cells were subjected to a range of pCO 2 from ambient to 993 µatm. We measured phytoplankton response in terms of cell size, cellular carbohydrate content, and elemental, pigment and fatty acid composition and content. We observed few changes in phytoplankton biochemistry with increasing CO 2 concentration which were species-specific and predominantly included differences in the fatty acid composition. The C:N ratio was unaffected by CO 2 concentration in the three species, while carbohydrate content decreased in Pyramimonas gelidicola, but increased in Phaeocystis antarctica. We found a significant reduction in the content of nutritionally important polyunsaturated fatty acids in OPEN ACCESSWater 2014, 6 1841Pyramimonas gelidicola cultures under high CO 2 treatment, while cellular levels of the polyunsaturated fatty acid 20:5ω3, EPA, in Gymnodinium sp. increased. These changes in fatty acid profile could affect the nutritional quality of phytoplankton as food for grazers, however, further research is needed to identify the mechanisms for the observed species-specific changes and to improve our ability to extrapolate laboratory-based experiments on individual species to natural communities.

show abstract

Phosphatidic Acid Is a pH Biosensor That Links Membrane Biogenesis to Metabolism

Cited by 239 publications

References 20 publications

Lipin 2 Binds Phosphatidic Acid by the Electrostatic Hydrogen Bond Switch Mechanism Independent of Phosphorylation

Lipin 2 Binds Phosphatidic Acid by the Electrostatic Hydrogen Bond Switch Mechanism Independent of Phosphorylation

Comparative analyses of isoforms of the calcium-independent phosphatidylethanolamine N-acyltransferase PLAAT-1 in humans and mice

Species-Specific Variations in the Nutritional Quality of Southern Ocean Phytoplankton in Response to Elevated pCO2

Contact Info

Product

Resources

About