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Nuclear Lipid Signaling
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Nuclear Lipid Signaling

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 28020

Special Issue Editors

Dr. Irene Faenza

E-Mail Website
Guest Editor
Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy
Interests: osteosarcoma; signal transduction; nucleus; phosphoinositide signaling; cyclin D3; Akt; chemotherapeutic agents; differentiation; nuclear phosphoinositides
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Lucio Cocco

E-Mail Website
Guest Editor
Department of Biomedical Sciences, University of Bologna, 40126 Bologna, Italy
Interests: signal transduction; phospholipase C; inositol lipids; hematological malignancies; central nervous system and signaling

Special Issue Information

Dear Colleagues,

For the last 20 years, a large number of papers have hinted at the existence and significance of signaling events inside the nucleus, mediated by lipids and lipid metabolism. This signaling involves PLCs, DGKs, PLD, sphingolipid-related enzymes. Interestingly, alterations of the signaling machinery have been detected in a number of diseases and this opens an entirely new field of investigation. Even though a large amount of data is related to inositol lipid and inositide-related signaling, clear evidence show that DGKs play important role in nuclear function, sphingolipid metabolites are active in the nucleus and inositol phosphates are important in RNA export. Recently, it has been shown that nuclear translocation of PKCα isoenzyme is involved in neurogenic commitment of human neural crest-derived periodontal ligament stem cells.

These evidences prompted us to edit a comprehensive, as much as possible, special issue dealing with the signaling machineries that have been found and studied at the nuclear level.

In this context, we would like to invite review and original articles that focus on nuclear structure, presence of lipids in sunclear domains, lipid mediated signaling in both normal and pathological conditions. Additionally, articles showing how phospholipids in general and polyohosphoinositide in particular and/or their metabolizing enzymes directly affects the transcriptional machinery are welcome. Given that a particular interest has been raised by the fact that inositide and inositide-related nuclear signaling (i.e., PKCs translocation into the nucleus) play a role during growth and differentiation of progenitor/stem cells, manuscripts dealing with nuclear lipid signaling in progenitor/stem cells are welcome as well.

Dr. Irene Faenza
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (6 papers)

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Research

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10 pages, 1799 KiB  
Article
Nuclear Lipid Microdomains Regulate Daunorubicin Resistance in Hepatoma Cells
by Michela Codini, Carmela Conte, Samuela Cataldi, Cataldo Arcuri, Andrea Lazzarini, Maria Rachele Ceccarini, Federica Patria, Alessandro Floridi, Carmen Mecca, Francesco Saverio Ambesi-Impiombato, Tommaso Beccari, Francesco Curcio and Elisabetta Albi
Int. J. Mol. Sci. 2018, 19(11), 3424; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19113424 - 01 Nov 2018
Cited by 8 | Viewed by 3064
Abstract
Daunorubicin is an anticancer drug, and cholesterol is involved in cancer progression, but their relationship has not been defined. In this study, we developed a novel experimental model that utilizes daunorubicin, cholesterol, and daunorubicin plus cholesterol in the same cells (H35) to search [...] Read more.
Daunorubicin is an anticancer drug, and cholesterol is involved in cancer progression, but their relationship has not been defined. In this study, we developed a novel experimental model that utilizes daunorubicin, cholesterol, and daunorubicin plus cholesterol in the same cells (H35) to search for the role of nuclear lipid microdomains, rich in cholesterol and sphingomyelin, in drug resistance. We find that the daunorubicin induces perturbation of nuclear lipid microdomains, localized in the inner nuclear membrane, where active chromatin is anchored. As changes of sphingomyelin species in nuclear lipid microdomains depend on neutral sphingomyelinase activity, we extended our studies to investigate whether the enzyme is modulated by daunorubicin. Indeed the drug stimulated the sphingomyelinase activity that induced reduction of saturated long chain fatty acid sphingomyelin species in nuclear lipid microdomains. Incubation of untreated-drug cells with high levels of cholesterol resulted in the inhibition of sphingomyelinase activity with increased saturated fatty acid sphingomyelin species. In daunodubicin-treated cells, incubation with cholesterol reversed the action of the drug by acting via neutral sphingomyelinase. In conclusion, we suggest that cholesterol and sphingomyelin-forming nuclear lipid microdomains are involved in the drug resistance. Full article
(This article belongs to the Special Issue Nuclear Lipid Signaling)
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18 pages, 2773 KiB  
Article
Multiple Aspects of PIP2 Involvement in C. elegans Gametogenesis
by Livia Ulicna, Jana Rohozkova and Pavel Hozak
Int. J. Mol. Sci. 2018, 19(9), 2679; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19092679 - 10 Sep 2018
Cited by 2 | Viewed by 4354
Abstract
One of the most studied phosphoinositides is phosphatidylinositol 4,5-bisphosphate (PIP2), which localizes to the plasma membrane, nuclear speckles, small foci in the nucleoplasm, and to the nucleolus in mammalian cells. Here, we show that PIP2 also localizes to the nucleus in prophase I, [...] Read more.
One of the most studied phosphoinositides is phosphatidylinositol 4,5-bisphosphate (PIP2), which localizes to the plasma membrane, nuclear speckles, small foci in the nucleoplasm, and to the nucleolus in mammalian cells. Here, we show that PIP2 also localizes to the nucleus in prophase I, during the gametogenesis of C. elegans hermaphrodite. The depletion of PIP2 by type I PIP kinase (PPK-1) kinase RNA interference results in an altered chromosome structure and leads to various defects during meiotic progression. We observed a decreased brood size and aneuploidy in progeny, defects in synapsis, and crossover formation. The altered chromosome structure is reflected in the increased transcription activity of a tightly regulated process in prophase I. To elucidate the involvement of PIP2 in the processes during the C. elegans development, we identified the PIP2-binding partners, leucine-rich repeat (LRR-1) protein and proteasome subunit beta 4 (PBS-4), pointing to its involvement in the ubiquitin–proteasome pathway. Full article
(This article belongs to the Special Issue Nuclear Lipid Signaling)
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Review

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20 pages, 4313 KiB  
Review
Nuclear Phosphoinositides: Their Regulation and Roles in Nuclear Functions
by R. Fiume, I. Faenza, B. Sheth, A. Poli, M.C. Vidalle, C. Mazzetti, S.H. Abdul, F. Campagnoli, M. Fabbrini, S.T. Kimber, G.A. Mariani, J. Xian, M.V. Marvi, S. Mongiorgi, Z. Shah and N. Divecha
Int. J. Mol. Sci. 2019, 20(12), 2991; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20122991 - 19 Jun 2019
Cited by 36 | Viewed by 4545
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Nuclear Lipid Signaling)
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17 pages, 578 KiB  
Review
Phosphatidylinositol 5 Phosphate (PI5P): From Behind the Scenes to the Front (Nuclear) Stage
by Alessandro Poli, Antonio Enrico Zaurito, Shidqiyyah Abdul-Hamid, Roberta Fiume, Irene Faenza and Nullin Divecha
Int. J. Mol. Sci. 2019, 20(9), 2080; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20092080 - 27 Apr 2019
Cited by 24 | Viewed by 5538
Abstract
Phosphatidylinositol (PI)-related signaling plays a pivotal role in many cellular aspects, including survival, cell proliferation, differentiation, DNA damage, and trafficking. PI is the core of a network of proteins represented by kinases, phosphatases, and lipases which are able to add, remove or hydrolyze [...] Read more.
Phosphatidylinositol (PI)-related signaling plays a pivotal role in many cellular aspects, including survival, cell proliferation, differentiation, DNA damage, and trafficking. PI is the core of a network of proteins represented by kinases, phosphatases, and lipases which are able to add, remove or hydrolyze PI, leading to different phosphoinositide products. Among the seven known phosphoinositides, phosphatidylinositol 5 phosphate (PI5P) was the last to be discovered. PI5P presence in cells is very low compared to other PIs. However, much evidence collected throughout the years has described the role of this mono-phosphoinositide in cell cycles, stress response, T-cell activation, and chromatin remodeling. Interestingly, PI5P has been found in different cellular compartments, including the nucleus. Here, we will review the nuclear role of PI5P, describing how it is synthesized and regulated, and how changes in the levels of this rare phosphoinositide can lead to different nuclear outputs. Full article
(This article belongs to the Special Issue Nuclear Lipid Signaling)
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11 pages, 1016 KiB  
Review
Phosphoinositide 3 Kinase Signaling in Human Stem Cells from Reprogramming to Differentiation: A Tale in Cytoplasmic and Nuclear Compartments
by Giulia Ramazzotti, Stefano Ratti, Roberta Fiume, Matilde Yung Follo, Anna Maria Billi, Isabella Rusciano, Eric Owusu Obeng, Lucia Manzoli, Lucio Cocco and Irene Faenza
Int. J. Mol. Sci. 2019, 20(8), 2026; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20082026 - 24 Apr 2019
Cited by 22 | Viewed by 5873
Abstract
Stem cells are undifferentiated cells that can give rise to several different cell types and can self-renew. Given their ability to differentiate into different lineages, stem cells retain huge therapeutic potential for regenerative medicine. Therefore, the understanding of the signaling pathways involved in [...] Read more.
Stem cells are undifferentiated cells that can give rise to several different cell types and can self-renew. Given their ability to differentiate into different lineages, stem cells retain huge therapeutic potential for regenerative medicine. Therefore, the understanding of the signaling pathways involved in stem cell pluripotency maintenance and differentiation has a paramount importance in order to understand these biological processes and to develop therapeutic strategies. In this review, we focus on phosphoinositide 3 kinase (PI3K) since its signaling pathway regulates many cellular processes, such as cell growth, proliferation, survival, and cellular transformation. Precisely, in human stem cells, the PI3K cascade is involved in different processes from pluripotency and induced pluripotent stem cell (iPSC) reprogramming to mesenchymal and oral mesenchymal differentiation, through different and interconnected mechanisms. Full article
(This article belongs to the Special Issue Nuclear Lipid Signaling)
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7 pages, 579 KiB  
Review
Dynamic Protein S-Acylation in Plants
by Lihua Zheng, Peng Liu, Qianwen Liu, Tao Wang and Jiangli Dong
Int. J. Mol. Sci. 2019, 20(3), 560; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20030560 - 29 Jan 2019
Cited by 21 | Viewed by 3925
Abstract
Lipid modification is an important post-translational modification. S-acylation is unique among lipid modifications, as it is reversible and has thus attracted much attention. We summarize some proteins that have been shown experimentally to be S-acylated in plants. Two of these S-acylated proteins have [...] Read more.
Lipid modification is an important post-translational modification. S-acylation is unique among lipid modifications, as it is reversible and has thus attracted much attention. We summarize some proteins that have been shown experimentally to be S-acylated in plants. Two of these S-acylated proteins have been matched to the S-acyl transferase. More importantly, the first protein thioesterase with de-S-acylation activity has been identified in plants. This review shows that S-acylation is important for a variety of different functions in plants and that there are many unexplored aspects of S-acylation in plants. Full article
(This article belongs to the Special Issue Nuclear Lipid Signaling)
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