Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells

Yu Ja Huang, Paula Schiapparelli, Kristen Kozielski, Jordan Green, Emily Lavell, Hugo Guerrero-Cazares, Alfredo Quinones-Hinojosa, Peter Searson

Research output: Contribution to journalArticle

Abstract

Endogenous electric fields modulate many physiological processes by promoting directional migration, a process known as galvanotaxis. Despite the importance of galvanotaxis in development and disease, the mechanism by which cells sense and migrate directionally in an electric field remains unknown. Here, we show that electrophoresis of cell surface heparan sulfate (HS) critically regulates this process. HS was found to be localized at the anode-facing side in fetal neural progenitor cells (fNPCs), fNPCderived astrocytes and brain tumor-initiating cells (BTICs), regardless of their direction of galvanotaxis. Enzymatic removal of HS and other sulfated glycosaminoglycans significantly abolished or reversed the cathodic response seen in fNPCs and BTICs. Furthermore, Slit2, a chemorepulsive ligand, was identified to be colocalized with HS in forming a ligand gradient across cellular membranes. Using both imaging and genetic modification, we propose a novel mechanism for galvanotaxis in which electrophoretic localization of HS establishes cell polarity by functioning as a co-receptor and provides repulsive guidance through Slit-Robo signaling.

LanguageEnglish (US)
Pages2459-2467
Number of pages9
JournalJournal of Cell Science
Volume130
Issue number15
DOIs
StatePublished - Aug 1 2017

Fingerprint

Heparitin Sulfate
Neuroglia
Electrophoresis
Cell Membrane
Neoplastic Stem Cells
A73025
Brain Neoplasms
Stem Cells
Physiological Phenomena
Ligands
Cell Polarity
Astrocytes
Electrodes
Membranes

Keywords

  • Brain tumor-initiating cells
  • Electrophoresis
  • Galvanotaxis
  • Heparan sulfate

ASJC Scopus subject areas

  • Cell Biology

Cite this

Huang, Y. J., Schiapparelli, P., Kozielski, K., Green, J., Lavell, E., Guerrero-Cazares, H., ... Searson, P. (2017). Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells. Journal of Cell Science, 130(15), 2459-2467. DOI: 10.1242/jcs.203752

Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells. / Huang, Yu Ja; Schiapparelli, Paula; Kozielski, Kristen; Green, Jordan; Lavell, Emily; Guerrero-Cazares, Hugo; Quinones-Hinojosa, Alfredo; Searson, Peter.

In: Journal of Cell Science, Vol. 130, No. 15, 01.08.2017, p. 2459-2467.

Research output: Contribution to journalArticle

Huang, YJ, Schiapparelli, P, Kozielski, K, Green, J, Lavell, E, Guerrero-Cazares, H, Quinones-Hinojosa, A & Searson, P 2017, 'Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells' Journal of Cell Science, vol. 130, no. 15, pp. 2459-2467. DOI: 10.1242/jcs.203752
Huang YJ, Schiapparelli P, Kozielski K, Green J, Lavell E, Guerrero-Cazares H et al. Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells. Journal of Cell Science. 2017 Aug 1;130(15):2459-2467. Available from, DOI: 10.1242/jcs.203752
Huang, Yu Ja ; Schiapparelli, Paula ; Kozielski, Kristen ; Green, Jordan ; Lavell, Emily ; Guerrero-Cazares, Hugo ; Quinones-Hinojosa, Alfredo ; Searson, Peter. / Electrophoresis of cell membrane heparan sulfate regulates galvanotaxis in glial cells. In: Journal of Cell Science. 2017 ; Vol. 130, No. 15. pp. 2459-2467
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