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Directing neuronal signaling through cell-surface glycan engineering.

Pulsipher A, Griffin ME, Stone SE, Brown JM, Hsieh-Wilson LC - J. Am. Chem. Soc. (2014)

Bottom Line: The ability to tailor plasma membranes with specific glycans may enable the control of signaling events that are critical for proper development and function.Neurons engineered to display CS-E-enriched polysaccharides exhibited increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth.This approach provides a facile, general route to tailor cell membranes with biologically active glycans and demonstrates the potential to direct important cellular events through cell-surface glycan engineering.

View Article: PubMed Central - PubMed

Affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology and Howard Hughes Medical Institute , 1200 East California Boulevard, Pasadena, California 91125, United States.

ABSTRACT
The ability to tailor plasma membranes with specific glycans may enable the control of signaling events that are critical for proper development and function. We report a method to modify cell surfaces with specific sulfated chondroitin sulfate (CS) glycosaminoglycans using chemically modified liposomes. Neurons engineered to display CS-E-enriched polysaccharides exhibited increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth. This approach provides a facile, general route to tailor cell membranes with biologically active glycans and demonstrates the potential to direct important cellular events through cell-surface glycan engineering.

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Presentation of CS-E polysaccharides on neuronal cellsurfacesstimulates neurite outgrowth. (A) Representative images and (B) quantificationof neurite outgrowth for neurons treated with unmodified liposomesor liposomes displaying CS-A-, CS-C-, or CS-E-enriched polysaccharides.Neurite outgrowth was normalized and plotted relative to untreatedneurons. Data represent mean ± SEM (*P <0.05) from at least three experiments. See SI for details.
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fig4: Presentation of CS-E polysaccharides on neuronal cellsurfacesstimulates neurite outgrowth. (A) Representative images and (B) quantificationof neurite outgrowth for neurons treated with unmodified liposomesor liposomes displaying CS-A-, CS-C-, or CS-E-enriched polysaccharides.Neurite outgrowth was normalized and plotted relative to untreatedneurons. Data represent mean ± SEM (*P <0.05) from at least three experiments. See SI for details.

Mentions: To circumvent this problem,we repeated the outgrowth assays withmultiple additions of liposomes every 8 h over a 24-h period. Underthese conditions, we found that cell-surface presentation of CS-Epolysaccharides significantly enhanced neurite outgrowth by 36.3 ±3.3% relative to untreated neurons (Figures 4 and S4, 10% dodecanone). As expected,neurons displaying CS-A or CS-C polysaccharides showed minimal neuriteoutgrowth when compared to untreated neurons (10.8 ± 4.8% and1.3 ± 1.8%, respectively). As a further control, dodecanone-containingliposomes were reacted with CS-E polysaccharides lacking the aminooxyfunctionality and then incubated with the cells. No difference inneurite outgrowth was observed relative to untreated neurons.


Directing neuronal signaling through cell-surface glycan engineering.

Pulsipher A, Griffin ME, Stone SE, Brown JM, Hsieh-Wilson LC - J. Am. Chem. Soc. (2014)

Presentation of CS-E polysaccharides on neuronal cellsurfacesstimulates neurite outgrowth. (A) Representative images and (B) quantificationof neurite outgrowth for neurons treated with unmodified liposomesor liposomes displaying CS-A-, CS-C-, or CS-E-enriched polysaccharides.Neurite outgrowth was normalized and plotted relative to untreatedneurons. Data represent mean ± SEM (*P <0.05) from at least three experiments. See SI for details.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120997&req=5

fig4: Presentation of CS-E polysaccharides on neuronal cellsurfacesstimulates neurite outgrowth. (A) Representative images and (B) quantificationof neurite outgrowth for neurons treated with unmodified liposomesor liposomes displaying CS-A-, CS-C-, or CS-E-enriched polysaccharides.Neurite outgrowth was normalized and plotted relative to untreatedneurons. Data represent mean ± SEM (*P <0.05) from at least three experiments. See SI for details.
Mentions: To circumvent this problem,we repeated the outgrowth assays withmultiple additions of liposomes every 8 h over a 24-h period. Underthese conditions, we found that cell-surface presentation of CS-Epolysaccharides significantly enhanced neurite outgrowth by 36.3 ±3.3% relative to untreated neurons (Figures 4 and S4, 10% dodecanone). As expected,neurons displaying CS-A or CS-C polysaccharides showed minimal neuriteoutgrowth when compared to untreated neurons (10.8 ± 4.8% and1.3 ± 1.8%, respectively). As a further control, dodecanone-containingliposomes were reacted with CS-E polysaccharides lacking the aminooxyfunctionality and then incubated with the cells. No difference inneurite outgrowth was observed relative to untreated neurons.

Bottom Line: The ability to tailor plasma membranes with specific glycans may enable the control of signaling events that are critical for proper development and function.Neurons engineered to display CS-E-enriched polysaccharides exhibited increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth.This approach provides a facile, general route to tailor cell membranes with biologically active glycans and demonstrates the potential to direct important cellular events through cell-surface glycan engineering.

View Article: PubMed Central - PubMed

Affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology and Howard Hughes Medical Institute , 1200 East California Boulevard, Pasadena, California 91125, United States.

ABSTRACT
The ability to tailor plasma membranes with specific glycans may enable the control of signaling events that are critical for proper development and function. We report a method to modify cell surfaces with specific sulfated chondroitin sulfate (CS) glycosaminoglycans using chemically modified liposomes. Neurons engineered to display CS-E-enriched polysaccharides exhibited increased activation of neurotrophin-mediated signaling pathways and enhanced axonal growth. This approach provides a facile, general route to tailor cell membranes with biologically active glycans and demonstrates the potential to direct important cellular events through cell-surface glycan engineering.

Show MeSH
Related in: MedlinePlus