Diacylglycerol kinases in membrane trafficking

Xie, Shuwei; Naslavsky, Naava; Caplan, Steven H

doi:10.1080/21592799.2015.1078431

Cited by 28 publications

(26 citation statements)

References 124 publications

(129 reference statements)

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“…Of particular importance for the present study is membrane trafficking. Recent studies indicate a role played by DAG and PA in the regulation of membrane trafficking, which suggests that DGK can also play a role in this biological function (50). Of all mammalian DGK isoforms, DGK⑀ is the one with the greatest likelihood to mediate membrane trafficking due to its role in the PI cycle.…”

Section: Membrane Sites Of High Gaussian Curvature Regulate Dgk⑀mentioning

confidence: 99%

Membrane curvature allosterically regulates the phosphatidylinositol cycle, controlling its rate and acyl-chain composition of its lipid intermediates

Bozelli

Jennings

Black

et al. 2018

Journal of Biological Chemistry

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Edited by Paul E. FraserSignaling events at membranes are often mediated by membrane lipid composition or membrane physical properties. These membrane properties could act either by favoring the membrane binding of downstream effectors or by modulating their activity. Several proteins can sense/generate membrane physical curvature (i.e. shape). However, the modulation of the activity of enzymes by a membrane's shape has not yet been reported. Here, using a cell-free assay with purified diacylglycerol kinase ⑀ (DGK⑀) and liposomes, we studied the activity and acyl-chain specificity of an enzyme of the phosphatidylinositol (PI) cycle, DGK⑀. By systematically varying the model membrane lipid composition and physical properties, we found that DGK⑀ has low activity and lacks acyl-chain specificity in locally flat membranes, regardless of the lipid composition. On the other hand, these enzyme properties were greatly enhanced in membrane structures with a negative Gaussian curvature. We also found that this is not a consequence of preferential binding of the enzyme to those structures, but rather is due to a curvature-mediated allosteric regulation of DGK⑀ activity and acylchain specificity. Moreover, in a fine-tuned interplay between the enzyme and the membrane, DGK⑀ favored the formation of structures with greater Gaussian curvature. DGK⑀ does not bear a regulatory domain, and these findings reveal the importance of membrane curvature in regulating DGK⑀ activity and acyl-chain specificity. Hence, this study highlights that a hierarchic coupling of membrane physical property and lipid composition synergistically regulates membrane signaling events. We propose that this regulatory mechanism of membrane-associated enzyme activity is likely more common than is currently appreciated.

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Section: Membrane Sites Of High Gaussian Curvature Regulate Dgk⑀mentioning

confidence: 99%

Membrane curvature allosterically regulates the phosphatidylinositol cycle, controlling its rate and acyl-chain composition of its lipid intermediates

Bozelli

Jennings

Black

et al. 2018

Journal of Biological Chemistry

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“…While PLDs are well known to be associated with PA production for exocytosis, more recently, the DGKs are proving to play significant roles in both PA and DAG signalling underpinning exocytosis . DGKs are widely evolutionarily conserved and their roles in PA production have been studied in bacteria , plants , multicellular organisms including drosophila , Caenorhabditis elegans and apicomplexan parasites .…”

Section: Production Of Pa For Membrane Signallingmentioning

confidence: 99%

“…DGKs are widely evolutionarily conserved and their roles in PA production have been studied in bacteria , plants , multicellular organisms including drosophila , Caenorhabditis elegans and apicomplexan parasites . It is, however, the mammalian DGK enzymes that are the best characterised to date with 10 known isoforms . These isoforms have been identified through differences in their regulatory and accessory domains and have established tissue and substrate specificity within mammalian cells as outlined in Table .…”

Section: Production Of Pa For Membrane Signallingmentioning

confidence: 99%

A central role for phosphatidic acid as a lipid mediator of regulated exocytosis in apicomplexa

Bullen

Soldati‐Favre

2016

FEBS Letters

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Edited by Wilhelm JustLipids are commonly known for the structural roles they play, however, the specific contribution of different lipid classes to wide-ranging signalling pathways is progressively being unravelled. Signalling lipids and their associated effector proteins are emerging as significant contributors to a vast array of effector functions within cells, including essential processes such as membrane fusion and vesicle exocytosis. Many phospholipids have signalling capacity, however, this review will focus on phosphatidic acid (PA) and the enzymes implicated in its production from diacylglycerol (DAG) and phosphatidylcholine (PC): DGK and PLD respectively. PA is a negatively charged, coneshaped lipid identified as a key mediator in specific membrane fusion and vesicle exocytosis events in a variety of mammalian cells, and has recently been implicated in specialised secretory organelle exocytosis in apicomplexan parasites. This review summarises the recent work implicating a role for PA regulation in exocytosis in various cell types. We will discuss how these signalling events are linked to pathogenesis in the phylum Apicomplexa.

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“…71 As endocytic trafficking is becoming increasingly recognized as a possible mechanism(s) of AD pathogenesis, examining the role of other endocytic trafficking regulators such as diacylglycerol kinase, Eps15 homology domain and molecules interacting with CasL-like1 (MICAL-L1) in both processing and release of APP via the exosomes can be developed as future areas of research that will provide valuable insights into the pathogenesis of AD. 76, 77, 78 Interestingly, aggregated tau protein has also been found to be present in the exosomes in both the in vitro taupathy models as well as in the cerebrospinal fluids of early Alzheimer's patients. 68 It is worth noting that microglia have an important role in spreading both A β and tau through the EVs.…”

Section: Alzheimer's Disease and Evsmentioning

confidence: 99%

Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on HIV-associated neurological complications

Lü

Cai

et al. 2016

Cell Death Dis

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Exosomes are membrane-enriched extracellular vesicles with a proposed diameter in the range of 30–100 nm. They are released during both normal homeostasis as well as under pathological conditions by most cell types. In recent years, there has been robust interest in the study of these vesicles as conduits for the delivery of information between cells in both analogous as well as disparate tissues. Their ability to transport specialized cargo including signaling mediators, proteins, messenger RNA and miRNAs characterizes these vesicles as primary facilitators of cell-to-cell communication and regulation. Exosomes have also been demonstrated to have important roles in the field of cancer biology and metastasis. More recently, their role in several neurodegenerative disorders has been gaining increased momentum as these particles have been shown to promote the spread of toxic factors such as amyloid beta and prions, adding further validity to their role as important regulators of disease pathogenesis. This review briefly summarizes current findings and thoughts on exosome biology in the context of neurodegenerative disorders and the manipulation of these particles for the development of potential therapeutic strategies.

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Diacylglycerol kinases in membrane trafficking

Cited by 28 publications

References 124 publications

Membrane curvature allosterically regulates the phosphatidylinositol cycle, controlling its rate and acyl-chain composition of its lipid intermediates

Membrane curvature allosterically regulates the phosphatidylinositol cycle, controlling its rate and acyl-chain composition of its lipid intermediates

A central role for phosphatidic acid as a lipid mediator of regulated exocytosis in apicomplexa

Emerging roles of extracellular vesicles in neurodegenerative disorders: focus on HIV-associated neurological complications

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