Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow

Watanabe, Hiroshi; Okahara, Kyohei; Naito-Matsui, Yuko; Abe, Mitsuhiro; Go, Shinji; Inokuchi, Jin-ichi; Okazaki, Toshiro; Kobayashi, Toshihide; Kozutsumi, Yasunori; Oka, Shogo; Takematsu, Hiromu

doi:10.1091/mbc.e15-08-0555

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…An interesting phenomenon was observed and circumvented prior to tracking: after cell surface Sia was completely removed by sialidase, the lipid raft-specific Sia signal markedly decreased, as was the lipid raft-specific protein labeling signal (Figures S8 and S9). This finding may be associated with the identity of the monosaccharide at the GM1 terminus of the CTxB ligand, that is, α-2,3-Sia, whereas the decrease in protein signal is primarily due to the cleavage of Sia disrupting the binding of CTxB to the lipid raft . The sialidase concentration did not affect the binding of CTxB to GM1 when the Sia update was tracked using the MPL method (second row of Figure , Figures S9 and S10).…”

Section: Resultsmentioning

confidence: 98%

“…This finding may be associated with the identity of the monosaccharide at the GM1 terminus of the CTxB ligand, that is, α-2,3-Sia, whereas the decrease in protein signal is primarily due to the cleavage of Sia disrupting the binding of CTxB to the lipid raft. 48 The sialidase concentration did not affect the binding of CTxB to GM1 when the Sia update was tracked using the MPL method (second row of Figure 3, Figures S9 and S10). After the appropriate release of Sia from the cell surface, lipid raftspecific Sia levels declined sharply.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Multifunctional Proximity Labeling Strategy for Lipid Raft-Specific Sialic Acid Tracking and Engineering

Guo,

Wang,

Jiang

et al. 2023

Bioconjugate Chem.

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Lipid raft-specific glycosylation has been implicated in many biological processes, including intracellular trafficking, cell adhesion, signal transduction, and host–pathogen interactions. The major predicament in lipid raft-specific glycosylation research is the unavailability of tools for tracking and manipulating glycans on lipid rafts at the microstructural level. To overcome this challenge, we developed a multifunctional proximity labeling (MPL) platform that relies on cholera toxin B subunit to localize horseradish peroxidase on lipid rafts. In addition to the prevailing electron-rich amino acids, modified sialic acid was included in the horseradish peroxidase-mediated proximity labeling substrate via purposefully designed chemical transformation reactions. In combination with sialic acid editing, the self-renewal of lipid raft-specific sialic acid was visualized. The MPL method enabled tracking of lipid raft dynamics under methyl-β-cyclodextrin and mevinolin treatments; in particular, the alteration of lipid rafts markedly affected cell migration. Furthermore, we embedded functional molecules into the method and implemented raft-specific sialic acid gradient engineering. Our novel strategy presents opportunities for tailoring lipid raft-specific sialic acids, thereby regulating interactions associated with lipid raft regions (such as cell–virus and cell–microenvironment interactions), and can aid in the development of lipid raft-based therapeutic regimens for tumors.

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Section: Resultsmentioning

confidence: 98%

Section: ■ Results and Discussionmentioning

confidence: 99%

Multifunctional Proximity Labeling Strategy for Lipid Raft-Specific Sialic Acid Tracking and Engineering

Guo,

Wang,

Jiang

et al. 2023

Bioconjugate Chem.

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“…LysoSM can act on G-protein-coupled receptors (S1PRs) [92,99]. On the other hand, GalSph may alter the lipid composition of plasma membranes and, as a consequence, affect signaling pathways that depend on lipid rafts [165] and/or tyrosine kinase receptors [155].…”

Section: Discussionmentioning

confidence: 99%

Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer

Dubot

Astudillo

Therville

et al. 2022

Cancers

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Sphingolipids play a key structural role in cellular membranes and/or act as signaling molecules. Inherited defects of their catabolism lead to lysosomal storage diseases called sphingolipidoses. Although progress has been made toward a better understanding of their pathophysiology, several issues still remain unsolved. In particular, whether lysosphingolipids, the deacylated form of sphingolipids, both of which accumulate in these diseases, are simple biomarkers or play an instrumental role is unclear. In the meanwhile, evidence has been provided for a high risk of developing malignancies in patients affected with Gaucher disease, the most common sphingolipidosis. This article aims at analyzing the potential involvement of lysosphingolipids in cancer. Knowledge about lysosphingolipids in the context of lysosomal storage diseases is summarized. Available data on the nature and prevalence of cancers in patients affected with sphingolipidoses are also reviewed. Then, studies investigating the biological effects of lysosphingolipids toward pro or antitumor pathways are discussed. Finally, original findings exploring the role of glucosylsphingosine in the development of melanoma are presented. While this lysosphingolipid may behave like a protumorigenic agent, further investigations in appropriate models are needed to elucidate the role of these peculiar lipids, not only in sphingolipidoses but also in malignant diseases in general.

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“…Indeed, it is of interest that knockout models of the G‐protein‐coupled receptor 4 (GPR4) receptor, another member of this subfamily, show formative abnormalities of vascular networks . However, latterly, T‐cell death‐associated gene 8 has been reported to be unequivocally dispensable for psychosine‐induced formation of multinucleated cells , and alternative mechanisms have been implicated, with inhibition of cytokinesis by β‐galactosylsphingosine being associated with clustering of sphingomyelin at the cell surface, as well as impaired generation of phosphatidylinositol 4,5‐bisphosphate at the cleavage furrow in cultured cells ; as both of these steps are critical accompaniments of cytokinesis, another cytological explanation for the observed polyploidy is available.…”

Section: Discussionmentioning

confidence: 99%

Reduced cerebral vascularization in experimental neuronopathic Gaucher disease

Smith

Fuller

Saville

et al. 2017

The Journal of Pathology

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The glycosphingolipidosis, Gaucher disease, in which a range of neurological manifestations occur, results from a deficiency of acid -glucocerebrosidase, with subsequent accumulation of -glucocerebroside, its upstream substrates, and the non-acylated congener -glucosylsphingosine. However, the mechanisms by which end-organ dysfunction arise are poorly understood. Here, we report strikingly diminished cerebral microvascular density in a murine model of disease, and provide a detailed analysis of the accompanying cerebral glycosphingolipidome in these animals, with marked elevations of -glucosylsphingosine. Further in vitro studies confirmed a concentration-dependent impairment of endothelial cytokinesis upon exposure to quasi-pathological concentrations of -glucosylsphingosine. These findings support a premise for pathogenic disruption of cerebral angiogenesis as an end-organ effect, with potential for therapeutic modulation in neuronopathic Gaucher disease.

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Psychosine-triggered endomitosis is modulated by membrane sphingolipids through regulation of phosphoinositide 4,5-bisphosphate production at the cleavage furrow

Cited by 8 publications

References 57 publications

Multifunctional Proximity Labeling Strategy for Lipid Raft-Specific Sialic Acid Tracking and Engineering

Multifunctional Proximity Labeling Strategy for Lipid Raft-Specific Sialic Acid Tracking and Engineering

Potential Role of Sphingolipidoses-Associated Lysosphingolipids in Cancer

Reduced cerebral vascularization in experimental neuronopathic Gaucher disease

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