Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

Pituch, Katarzyna C.; Moyano, Ana Lis; Lopez-Rosas, Aurora; Marottoli, Felecia M.; Li, Guannan; Hu, Chenqi; Breemen, Richard B. van; Je, Månsson; Givogri, Maria I.

doi:10.1074/jbc.m115.636498

Cited by 36 publications

(40 citation statements)

References 100 publications

(90 reference statements)

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“…It has been reported that PDGFRα can be secreted through oligodendrocyte‐derived EVs during development . However, the mechanism of PDGFRα release through EVs, and of RTKs in general, remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that PDGFRa can be secreted through oligodendrocyte-derived EVs during development. (40) However, the mechanism of PDGFRa release through EVs, and of RTKs in general, remains unknown. Some studies demonstrate that association to RalA and RalB proteins (41) or posttranslational modifications such as ISGylation (39) and ubiquitination (32) are essential for general EV secretion.…”

Section: Discussionmentioning

confidence: 99%

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Hepatic stellate cell–derived platelet‐derived growth factor receptor‐alpha‐enriched extracellular vesicles promote liver fibrosis in mice through SHP2

Kostallari¹,

Hirsova²,

Prašnická³

et al. 2018

Hepatology

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatic stellate cell–derived platelet‐derived growth factor receptor‐alpha‐enriched extracellular vesicles promote liver fibrosis in mice through SHP2

Kostallari¹,

Hirsova²,

Prašnická³

et al. 2018

Hepatology

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“…Activation of Akt via adrenal cortical hormones could promote oligodendrogenesis and the effect was abolished by inhibition of Akt (Cai et al 2014; Maki et al 2015). PDGFRα, transferrin and the thrombin receptor also can modulate the generation of OPCs through Akt signaling (Pérez et al 2013; Pituch et al 2015; Yoon et al 2015). …”

Section: Discussionmentioning

confidence: 99%

Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation

Safina

Schlitt

Romeo

et al. 2016

Glia

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The LDL family of receptors and its member LRP1 have classically been associated with a modulation of lipoprotein metabolism. Current studies, however, indicate diverse functions for this receptor in various aspects of cellular activities, including cell proliferation, migration, differentiation and survival. LRP1 is essential for normal neuronal function in the adult CNS, whereas the role of LRP1 in development remained unclear. Previously we have observed an upregulation of LewisX (LeX) glycosylated LRP1 in the stem cells of the developing cortex and demonstrated its importance for oligodendrocyte differentiation. In the current study we show that LeX-glycosylated LRP1 is also expressed in the stem cell compartment of the developing spinal cord and has broader functions in the developing CNS. We have investigated the basic properties of LRP1 conditional knockout on the neural stem/progenitor cells (NSPCs) from the cortex and the spinal cord, created by means of Cre-loxp mediated recombination in vitro. The functional status of LRP1-deficient cells has been studied using proliferation, differentiation and apoptosis assays. LRP1 deficient NSPCs from both CNS regions demonstrated altered differentiation profiles. Their differentiation capacity towards oligodendrocyte progenitor cells (OPCs), mature oligodendrocytes and neurons was reduced. In contrast, astrocyte differentiation was promoted. Moreover, LRP1 deletion had a negative effect on NSPCs proliferation and survival. Our observations suggest that LRP1 facilitates NSPCs differentiation via interaction with ApoE. Upon ApoE4 stimulation wild type NSPCs generated more oligodendrocytes, but LRP1 knockout cells showed no response. The effect of ApoE seems to be independent of cholesterol uptake, but is rather mediated by downstream MAPK and Akt activation.

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“…Sphingolipids such as sulfatides and psychosine, which are accumulated in metachromatic leukodystrophy (MLD) and Krabbe's disease, respectively, and are highly enriched in brain lipid rafts (White et al, ; Moyano et al, ), are good examples of potentially EV‐released neurotoxic lipids. For example, we showed that increased sulfatides in MLD neural precursors parallels the secretion of higher levels of PDGFRα, a key regulator of oligodendroglial proliferation and survival (Pituch et al, ). A direct role for sulfatides in this effect is under investigation (Moyano and Givogri, unpublished), but sulfatides have been found in EVs secreted by mature oligodendrocytes (Kramer‐Albers et al, ).…”

Section: Evs: Shuttling Toxins Within the Nervous System?mentioning

confidence: 99%

Port‐to‐port delivery: Mobilization of toxic sphingolipids via extracellular vesicles

Scesa

Moyano

Bongarzone

et al. 2016

J of Neuroscience Research

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The discovery that most cells produce extracellular vesicles (EVs) and release them in the extracellular milieu has spurred the idea that these membranous cargoes spread pathogenic mechanisms. In the brain, EVs may have multifold and important physiological functions, from deregulating synaptic activity, to promoting demyelination, to changes in microglial activity. The finding that small EVs (exosomes) contain α-synuclein and β-amyloid, among other pathogenic proteins, is an example of this notion, underlining their potential role in the brain of patients with Parkinson’s and Alzheimer’s diseases. Being membranous-vesicles, we speculate that EVs also have an intrinsic capacity to incorporate sphingolipids. In conditions where these lipids are elevated to toxic levels such as in Krabbe’s disease and Metachromatic leukodystrophy, EVs may contribute to spread disease from sick to healthy cells. In this essay, we discuss a working hypothesis that brain cells in sphingolipidoses clear some of the accumulated lipid material to attempt restoring cell homeostasis via EV secretion. We hypothesize that secreted sphingolipid-loaded EVs shuttle pathogenic lipids to cells that are not intrinsically affected, contributing to establishing non-cell autonomous defects.

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Dysfunction of Platelet-derived Growth Factor Receptor α (PDGFRα) Represses the Production of Oligodendrocytes from Arylsulfatase A-deficient Multipotential Neural Precursor Cells

Cited by 36 publications

References 100 publications

Hepatic stellate cell–derived platelet‐derived growth factor receptor‐alpha‐enriched extracellular vesicles promote liver fibrosis in mice through SHP2

Hepatic stellate cell–derived platelet‐derived growth factor receptor‐alpha‐enriched extracellular vesicles promote liver fibrosis in mice through SHP2

Low‐density lipoprotein receptor‐related protein 1 is a novel modulator of radial glia stem cell proliferation, survival, and differentiation

Port‐to‐port delivery: Mobilization of toxic sphingolipids via extracellular vesicles

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