Nuclear lipid microdomains regulate nuclear vitamin D<sub>3</sub>uptake and influence embryonic hippocampal cell differentiation

Bartoccini, Elisa; Marini, Francesca; Damaskopoulou, Eleni; Lazzarini, Remo; Cataldi, Samuela; Cascianelli, Giacomo; Garcia, Mercedes Gil; Albi, Elisabetta

doi:10.1091/mbc.e11-03-0196

Cited by 45 publications

(59 citation statements)

References 35 publications

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“…Recent studies suggest that nuclear lipids are organized into microdomains with similar characteristics to liquid ordered regions of the plasma membrane (Bartoccini et al, 2011), a proposal supported by our observation that nuclear Rac1 partially partitions into GM1-enriched cold detergent-resistant nuclear microdomains ( Figure 5A). Our proposal that Rac1 acts as a plasma membrane organizer through a mechanism dependent on the actin cytoskeleton (Navarro-Lé rida et al, 2012; Visa and Percipalle, 2010) can thus now be extended to the nucleus (Figures 5 and S3H).…”

Section: Discussionsupporting

confidence: 83%

Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion

et al. 2015

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Nuclear membrane microdomains are proposed to act as platforms for regulation of nuclear function, but little is known about the mechanisms controlling their formation. Organization of the plasma membrane is regulated by actin polymerization, and the existence of an actin pool in the nucleus suggests that a similar mechanism might operate here. We show that nuclear membrane organization and morphology are regulated by the nuclear level of active Rac1 through actin polymerization-dependent mechanisms. Rac1 nuclear export is mediated by two internal nuclear export signals and through its interaction with nucleophosmin-1 (B23), which acts as a Rac1 chaperone inside the nucleus. Rac1 nuclear accumulation alters the balance between cytosolic Rac1 and Rho, increasing RhoA signaling in the cytoplasm and promoting a highly invasive phenotype. Nuclear Rac1 shuttling is a finely tuned mechanism for controlling nuclear shape and organization and cell invasiveness.

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Section: Discussionsupporting

confidence: 83%

Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion

et al. 2015

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“…It attenuates Aβ peptide accumulation by stimulating phagocytosis of Aβ peptide probably by modulating transcription of Toll-like receptors and cytokines together with enhancing brain-to-blood efflux transport by increasing P-glycoprotein expression and likely by altering Amyloid Precursor Protein (APP) processing [88] and prevents the acetylcholine defect by increasing the activity of choline acetyltransferase (thus acetylcholine synthesis) in the brain [203]. Part of VDR is also located in lipid microdomains in the nuclear membrane [2], and this localization is modified by altering SL metabolism and has been associated with embryonic hippocampal cell differentiation. Neuroprotective actions of SLs, in particular S1P, and SLs, in particular S1P, could act synergistically on neuroprotection and/or neurogenesis in AD is still unknown and deserves further investigation.…”

Section: Cross Talk Between Vitamin D and Sphingolipid Metabolismmentioning

confidence: 99%

“…1-Alpha,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ), a known regulator of calcium and phosphorus homeostasis, has also important physiological effects on growth and differentiation in a variety of nonmalignant and malignant cell types [1][2][3][4] and a central role in host defense lacunae. Matrix degradation products are endocytosed from the central portion of the ruffled border, packaged into transcytotic vesicles and secreted from the functional secretory domain [37].…”

Section: Introductionmentioning

confidence: 99%

Vitamin D and Sphingolipids: Role in Bone and Neural System

Frati¹,

Gil²,

Pierucci³

et al. 2017

A Critical Evaluation of Vitamin D - Basic Overview

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Abstract1-Alpha,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is known to play an important physiological role on growth and differentiation in a variety of nonmalignant and malignant cell types through classical actions, mediated by its specific receptor (VDR), and nongenomic actions resulting in the activation of specific signalling pathways. Due to the broad distribution of Vitamin D Receptor (VDR) in many tissues and the ability of 1,25(OH) 2 D 3 to regulate fundamental processes, such as cell proliferation and differentiation, this steroid hormone has been suggested in the treatment of different diseases, from cancer to neurodegenerative diseases. In fact, structural 1,25(OH) 2 D 3 analogues, with weaker collateral effects, have recently entered in clinical trials. Other interesting molecules due to their pleiotropic actions are the bioactive sphingolipids (SLs), in particular ceramide (Cer) and sphingosine 1-phosphate (S1P). Cells maintain a dynamic balance of these metabolites since Cer and sphingoid bases mediate cell death, while S1P exerts mitogenic effects and promotes differentiation of several cell types including osteogenic and neural cells. The biological actions of 1,25(OH) 2 D 3 and SLs, in particular S1P, share many common effectors, including calcium regulation, growth factor expression, inflammatory cytokines, etc., but whether they could act synergistically is still unknown and deserves further investigation.

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“…In addition, NLMs regulate nuclear vitamin D3 uptake by influencing differentiation of embryonic hippocampal cells (11). In hepatoma cells, NLMs play a role as resting place of dexamethasone to delay cell proliferation (12).…”

Section: Introductionmentioning

confidence: 99%

Localization of nuclear actin in nuclear lipid microdomains of liver and hepatoma cells: Possible involvement of sphingomyelin metabolism

Cataldi

Lazzarini

Codini

et al. 2017

The EuroBiotech Journal

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Nuclear actin has been implicated in different nuclear functions. In this work, its localization in nuclear membrane, chromatin and nuclear lipid microdomains was investigated. The implication of sphingomyelin metabolism was studied.Nuclear membrane, chromatin and nuclear lipid microdomains were purified from hepatocyte nuclei and H35 human hepatoma cell nuclei. The presence of β-actin was analyzed with immunoblotting by using specific antibodies. Sphingomyelinase, sphingomyelin-synthase, and phosphatidylcholine-specific phospholipase C activities were assayed by using radioactivity sphingomyelin and phosphatidylcholine as substrate.The results showed that β-actin is localized in nuclear lipid microdomains and it increases in cancer cells. Evidence is provided to the difference of phosphatidylcholine and sphingomyelin metabolism in various subnuclear fractions of cancer cell nuclei compared with normal cells. Our findings show increase of sphingomyelin-synthase and inhibition of sphingomyelinase activity only in nuclear lipid microdomains.Nuclear lipid microdomains, constituted by phosphatidylcholine, sphingomyelin and cholesterol, play a role as platform for β-actin anchoring. Possible role of sphingomyelin metabolism in cancer cells is discussed.

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Nuclear lipid microdomains regulate nuclear vitamin D₃uptake and influence embryonic hippocampal cell differentiation

Cited by 45 publications

References 35 publications

Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion

Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion

Vitamin D and Sphingolipids: Role in Bone and Neural System

Localization of nuclear actin in nuclear lipid microdomains of liver and hepatoma cells: Possible involvement of sphingomyelin metabolism

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Nuclear lipid microdomains regulate nuclear vitamin D3uptake and influence embryonic hippocampal cell differentiation

Cited by 45 publications

References 35 publications

Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion

Rac1 Nucleocytoplasmic Shuttling Drives Nuclear Shape Changes and Tumor Invasion

Vitamin D and Sphingolipids: Role in Bone and Neural System

Localization of nuclear actin in nuclear lipid microdomains of liver and hepatoma cells: Possible involvement of sphingomyelin metabolism

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Nuclear lipid microdomains regulate nuclear vitamin D₃uptake and influence embryonic hippocampal cell differentiation