Phosphoinositides: multipurpose cellular lipids with emerging roles in cell death

Phan, Thanh Kha; Williams, Scott A.; Bindra, Guneet K.; Lay, Fung T.; Poon, Ivan K. H.; Hulett, Mark D.

doi:10.1038/s41418-018-0269-2

Cited by 39 publications

(36 citation statements)

References 118 publications

(162 reference statements)

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“…Target protein localisation occurs through specific lipid interaction motifs such as pleckstrin homology (PH) domains, Phox (PX) domains, FYVE domains or lysine arginine rich patches. PPIns regulate many cellular processes including membrane transport [2,4], ion channel function [5,6], cell adhesion, endo- and exo-cytosis [7], autophagy [8], transcription [1], RNA maturation [9] and cell survival [10] (Figure 1B). Importantly, many PPIns kinases and phosphatases are deregulated in various severe pathophysiological disorders such as cancer [11], myotubular myopathies [12] and Lowe syndrome [13].…”

Section: Introductionmentioning

confidence: 99%

Nuclear Phosphoinositides: Their Regulation and Roles in Nuclear Functions

Fiume

Faenza

Sheth

et al. 2019

IJMS

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Polyphosphoinositides (PPIns) are a family of seven lipid messengers that regulate a vast array of signalling pathways to control cell proliferation, migration, survival and differentiation. PPIns are differentially present in various sub-cellular compartments and, through the recruitment and regulation of specific proteins, are key regulators of compartment identity and function. Phosphoinositides and the enzymes that synthesise and degrade them are also present in the nuclear membrane and in nuclear membraneless compartments such as nuclear speckles. Here we discuss how PPIns in the nucleus are modulated in response to external cues and how they function to control downstream signalling. Finally we suggest a role for nuclear PPIns in liquid phase separations that are involved in the formation of membraneless compartments within the nucleus.

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Section: Introductionmentioning

confidence: 99%

Nuclear Phosphoinositides: Their Regulation and Roles in Nuclear Functions

Fiume

Faenza

Sheth

et al. 2019

IJMS

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“…This PI is a major component of the lipid bilayer. A recent study of Phan et al, (2019) added that PI is phosphorylated, and acts as a regulator of membrane trafficking, cytoskeleton interaction and signal transduction. Furthermore, previous work of Fujita and Kinoshita, (2012) reported that PI is a precursor of glycosyl-phosphatidylinositol (GPI), which is a conserved post-translational modification among the eukaryotes.…”

Section: Future Perspectivementioning

confidence: 99%

Lipid droplets formation and their effects on phosphatidylinositol level in yeasts

Mutijima

Basiony

Fujita

2020

Novel Research in Microbiology Journal

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Lipid droplets (LDs) are conserved specialized organelles that are surrounded by a single phospholipid layer, enclosing neutral lipids in form of triacylglycerol (TAG) and/or sterol ester. They are formed at the endoplasmic reticulum (ER), and stay connected to it in the yeast cell. These LDs mainly play major roles in lipid storage and homeostasis. Moreover, they have several functions in the yeast cell including; protein degradation, protein glycosylation, response to ER stress, in addition to providing substrate for energy metabolism and for membrane synthesis. In general, TAG and phosphatidylinositol (PI) synthesis share the same precursor; phosphatidic acid (PA), which controls their level. By the actions of lipases, phosphatases and/or kinases; one can act as a precursor for another, thus explaining the reason of their inverse correlation. TAG lipolysis is catalyzed by TAG lipases producing fatty acids and diacylglycerol (DAG). The DAG produced from lipolysis is phosphorylated by diacylglycerol kinase (Dgk1) to form PA. On the other hand, PA is a cell signaling molecule and once increased, it upregulates cytidine diphosphate diacylglycerol (CDP-DAG) pathway for the PI synthesis. Major TAG lipases are mainly localized in LD, whereas minor amounts of them are localized in ER. Once DAG is produced inside the LD, it is transferred to the ER by inheritance cortical ER protein, Ice2, for further reactions. The TAG and PI levels are also controlled by transcriptional regulation in response to inositol and zinc. The aim of this study was to clarify how LDs regulate lipid homeostasis in the yeast cell, and particularly focuses on the balance between TAG and PI.

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“…Phosphoinositides (PIs) represent a tiny component of the total phospholipid content in eukaryotic cell membranes, but they regulate numerous cellular activities such as cell adhesion [1], migration [2], apoptosis [3], vesicular trafficking [4], and post-translational modifications [5]. These processes are consistent with cancer-associated cellular mechanisms.…”

Section: Introductionmentioning

confidence: 98%

Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases

Fazio

Obeng

Rusciano

et al. 2020

IJMS

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An increasing number of reports suggests a significant involvement of the phosphoinositide (PI) cycle in cancer development and progression. Diacylglycerol kinases (DGKs) are very active in the PI cycle. They are a family of ten members that convert diacylglycerol (DAG) into phosphatidic acid (PA), two-second messengers with versatile cellular functions. Notably, some DGK isoforms, such as DGKα, have been reported to possess promising therapeutic potential in cancer therapy. However, further studies are needed in order to better comprehend their involvement in cancer. In this review, we highlight that DGKs are an essential component of the PI cycle that localize within several subcellular compartments, including the nucleus and plasma membrane, together with their PI substrates and that they are involved in mediating major cancer cell mechanisms such as growth and metastasis. DGKs control cancer cell survival, proliferation, and angiogenesis by regulating Akt/mTOR and MAPK/ERK pathways. In addition, some DGKs control cancer cell migration by regulating the activities of the Rho GTPases Rac1 and RhoA.

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Phosphoinositides: multipurpose cellular lipids with emerging roles in cell death

Cited by 39 publications

References 118 publications

Nuclear Phosphoinositides: Their Regulation and Roles in Nuclear Functions

Nuclear Phosphoinositides: Their Regulation and Roles in Nuclear Functions

Lipid droplets formation and their effects on phosphatidylinositol level in yeasts

Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases

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