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ARF6 Regulates Neuron Differentiation through Glucosylceramide Synthase

The small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in addition been shown to regulate neuron differentiation. Here we investigated whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the cellular lipid composition. We showed that knockdown of ARF... Full description

Journal Title: PLoS One Mar 2013, Vol.8(3), p.e60118
Main Author: Lu, Li
Other Authors: Ståhlman, Marcus , Rutberg, Mikael , Håversen, Liliana , Fogelstrand, Per , Andersson, Linda , Levin, Malin , Borén, Jan
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0060118
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title: ARF6 Regulates Neuron Differentiation through Glucosylceramide Synthase
format: Article
creator:
  • Lu, Li
  • Ståhlman, Marcus
  • Rutberg, Mikael
  • Håversen, Liliana
  • Fogelstrand, Per
  • Andersson, Linda
  • Levin, Malin
  • Borén, Jan
subjects:
  • Sweden
  • Laboratories
  • Lipid Composition
  • Clinical Medicine
  • Biochemistry
  • Neurochemistry
  • Ceramide
  • Guanosinetriphosphatase
  • Ribosylation
  • Biology
  • Endocytosis
  • Metabolism
  • Lipids
  • Kinases
  • Proteins
  • Differentiation
  • Plasmids
  • Neuroblastoma
  • Gene Expression
  • Medicine
ispartof: PLoS One, Mar 2013, Vol.8(3), p.e60118
description: The small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in addition been shown to regulate neuron differentiation. Here we investigated whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the cellular lipid composition. We showed that knockdown of ARF6 by siRNA in Neuro-2a cells increased neuronal outgrowth as expected. ARF6 knockdown also resulted in increased glucosylceramide levels and decreased sphingomyelin levels, but did not affect the levels of ceramide or phospholipids. We speculated that the ARF6 knockdown-induced increase in glucosylceramide was caused by an effect on glucosylceramide synthase and, in agreement, showed that ARF6 knockdown increased the mRNA levels and activity of glucosylceramide synthase. Finally, we showed that incubation of Neuro-2a cells with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) normalized the increased neuronal outgrowth induced by ARF6 knockdown....
language: eng
source:
identifier: E-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0060118
fulltext: fulltext_linktorsrc
issn:
  • 19326203
  • 1932-6203
url: Link


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titleARF6 Regulates Neuron Differentiation through Glucosylceramide Synthase
creatorLu, Li ; Ståhlman, Marcus ; Rutberg, Mikael ; Håversen, Liliana ; Fogelstrand, Per ; Andersson, Linda ; Levin, Malin ; Borén, Jan
ispartofPLoS One, Mar 2013, Vol.8(3), p.e60118
identifierE-ISSN: 19326203 ; DOI: 10.1371/journal.pone.0060118
subjectSweden ; Laboratories ; Lipid Composition ; Clinical Medicine ; Biochemistry ; Neurochemistry ; Ceramide ; Guanosinetriphosphatase ; Ribosylation ; Biology ; Endocytosis ; Metabolism ; Lipids ; Kinases ; Proteins ; Differentiation ; Plasmids ; Neuroblastoma ; Gene Expression ; Medicine
descriptionThe small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in addition been shown to regulate neuron differentiation. Here we investigated whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the cellular lipid composition. We showed that knockdown of ARF6 by siRNA in Neuro-2a cells increased neuronal outgrowth as expected. ARF6 knockdown also resulted in increased glucosylceramide levels and decreased sphingomyelin levels, but did not affect the levels of ceramide or phospholipids. We speculated that the ARF6 knockdown-induced increase in glucosylceramide was caused by an effect on glucosylceramide synthase and, in agreement, showed that ARF6 knockdown increased the mRNA levels and activity of glucosylceramide synthase. Finally, we showed that incubation of Neuro-2a cells with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) normalized the increased neuronal outgrowth induced by ARF6 knockdown....
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titleARF6 Regulates Neuron Differentiation through Glucosylceramide Synthase
descriptionThe small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in addition been shown to regulate neuron differentiation. Here we investigated whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the cellular lipid composition. We showed that knockdown of ARF6 by siRNA in Neuro-2a cells increased neuronal outgrowth as expected. ARF6 knockdown also resulted in increased glucosylceramide levels and decreased sphingomyelin levels, but did not affect the levels of ceramide or phospholipids. We speculated that the ARF6 knockdown-induced increase in glucosylceramide was caused by an effect on glucosylceramide synthase and, in agreement, showed that ARF6 knockdown increased the mRNA levels and activity of glucosylceramide synthase. Finally, we showed that incubation of Neuro-2a cells with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) normalized the increased neuronal outgrowth induced by ARF6 knockdown....
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titleARF6 Regulates Neuron Differentiation through Glucosylceramide Synthase
authorLu, Li ; Ståhlman, Marcus ; Rutberg, Mikael ; Håversen, Liliana ; Fogelstrand, Per ; Andersson, Linda ; Levin, Malin ; Borén, Jan
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6Ceramide
7Guanosinetriphosphatase
8Ribosylation
9Biology
10Endocytosis
11Metabolism
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13Kinases
14Proteins
15Differentiation
16Plasmids
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abstractThe small GTPase ADP ribosylation factor 6 (ARF6) mediates endocytosis and has in addition been shown to regulate neuron differentiation. Here we investigated whether ARF6 promotes differentiation of Neuro-2a neuronal cells by modifying the cellular lipid composition. We showed that knockdown of ARF6 by siRNA in Neuro-2a cells increased neuronal outgrowth as expected. ARF6 knockdown also resulted in increased glucosylceramide levels and decreased sphingomyelin levels, but did not affect the levels of ceramide or phospholipids. We speculated that the ARF6 knockdown-induced increase in glucosylceramide was caused by an effect on glucosylceramide synthase and, in agreement, showed that ARF6 knockdown increased the mRNA levels and activity of glucosylceramide synthase. Finally, we showed that incubation of Neuro-2a cells with the glucosylceramide synthase inhibitor D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) normalized the increased neuronal outgrowth induced by ARF6 knockdown....
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doi10.1371/journal.pone.0060118
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