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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.

Show MeSH
(A) CS polysaccharide structures used in thisstudy. n ≈ 110. (B) Strategy to remodel cellsurfaces with CS GAGsand control signaling pathways.
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fig1: (A) CS polysaccharide structures used in thisstudy. n ≈ 110. (B) Strategy to remodel cellsurfaces with CS GAGsand control signaling pathways.

Mentions: Glycosaminoglycans (GAGs) aresulfated, linear polysaccharides that participate in many fundamentalphysiological processes, including cell division, cancer metastasis,angiogenesis, and neuronal development.1−3 Increasing evidence suggeststhat GAGs interact with diverse proteins in a sulfation-dependentmanner and modulate cellular signaling events.3a,3b,4 For example, a specific sulfation motiffound on chondroitin sulfate GAGs (CS-E, Figure 1A) engages neurotrophin growth factors and their receptors, therebystimulating downstream signaling pathways to enhance neurite outgrowth.3a,4a Indeed, distinct sulfation patterns have been shown to modulatepathways involved in development,3b,3c,4c normal physiological function,4a,4b and disease.5 Thus, the ability to presentspecific GAG structures on cell surfaces could provide a novel approachto control key cellular events. Such a method may also acceleratestructure–function studies, as the complex, heterogeneous natureof GAGs on cell surfaces has hampered efforts to understand the rolesof specific sulfation motifs in vivo.


Directing neuronal signaling through cell-surface glycan engineering.

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

(A) CS polysaccharide structures used in thisstudy. n ≈ 110. (B) Strategy to remodel cellsurfaces with CS GAGsand control signaling pathways.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: (A) CS polysaccharide structures used in thisstudy. n ≈ 110. (B) Strategy to remodel cellsurfaces with CS GAGsand control signaling pathways.
Mentions: Glycosaminoglycans (GAGs) aresulfated, linear polysaccharides that participate in many fundamentalphysiological processes, including cell division, cancer metastasis,angiogenesis, and neuronal development.1−3 Increasing evidence suggeststhat GAGs interact with diverse proteins in a sulfation-dependentmanner and modulate cellular signaling events.3a,3b,4 For example, a specific sulfation motiffound on chondroitin sulfate GAGs (CS-E, Figure 1A) engages neurotrophin growth factors and their receptors, therebystimulating downstream signaling pathways to enhance neurite outgrowth.3a,4a Indeed, distinct sulfation patterns have been shown to modulatepathways involved in development,3b,3c,4c normal physiological function,4a,4b and disease.5 Thus, the ability to presentspecific GAG structures on cell surfaces could provide a novel approachto control key cellular events. Such a method may also acceleratestructure–function studies, as the complex, heterogeneous natureof GAGs on cell surfaces has hampered efforts to understand the rolesof specific sulfation motifs in vivo.

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