Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction

Anissa Kempf; Enrica Boda; Jessica C F Kwok; Rafael Fritz; Valentina Grande; Andrea M Kaelin; Zorica Ristic; Andre Schmandke; Antonio Schmandke; Bjoern Tews; James W Fawcett; Olivier Pertz; Annalisa Buffo; Martin E Schwab

doi:10.1016/j.devcel.2017.08.014

Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction

Dev Cell. 2017 Oct 9;43(1):24-34.e5. doi: 10.1016/j.devcel.2017.08.014. Epub 2017 Sep 21.

Authors

Affiliations

¹ Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, 8057 Zurich, Switzerland. Electronic address: anissa.kempf@cncb.ox.ac.uk.
² Department of Neuroscience, Neuroscience Institute Cavalieri Ottolenghi (NICO), Università degli Studi di Torino, Orbassano, Turin 10043, Italy.
³ John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Robinson Way, Cambridge CB2 0PY, UK.
⁴ Institute for Biochemistry and Genetics, Department of Biomedicine, University of Basel, 4058 Basel, Switzerland.
⁵ Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, 8057 Zurich, Switzerland.
⁶ Schaller Research Group at the University of Heidelberg and the German Cancer Research Center (DKFZ), Molecular Mechanisms of Tumor Invasion, 69120 Heidelberg, Germany.
⁷ Brain Research Institute, University of Zurich and Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH) Zurich, 8057 Zurich, Switzerland. Electronic address: schwab@hifo.uzh.ch.

PMID: 28943240
DOI: 10.1016/j.devcel.2017.08.014

Abstract

Heparan sulfate proteoglycans (HSPGs) critically modulate adhesion-, growth-, and migration-related processes. Here, we show that the transmembrane protein, Nogo-A, inhibits neurite outgrowth and cell spreading in neurons and Nogo-A-responsive cell lines via HSPGs. The extracellular, active 180 amino acid Nogo-A region, named Nogo-A-Δ20, binds to heparin and brain-derived heparan sulfate glycosaminoglycans (GAGs) but not to the closely related chondroitin sulfate GAGs. HSPGs are required for Nogo-A-Δ20-induced inhibition of adhesion, cell spreading, and neurite outgrowth, as well as for RhoA activation. Surprisingly, we show that Nogo-A-Δ20 can act via HSPGs independently of its receptor, Sphingosine-1-Phosphate receptor 2 (S1PR2). We thereby identify the HSPG family members syndecan-3 and syndecan-4 as functional receptors for Nogo-A-Δ20. Finally, we show in explant cultures ex vivo that Nogo-A-Δ20 promotes the migration of neuroblasts via HSPGs but not S1PR2.

Keywords: HSPG; RMS; SVZ; adhesion; migration; neuroblast; nogo-A; outgrowth; spreading; syndecan.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carrier Proteins / metabolism
Cell Line
Cell Movement / physiology*
Cell Shape / physiology*
Cells, Cultured
Heparan Sulfate Proteoglycans / metabolism*
Heparitin Sulfate / metabolism
Mice
Neurites / metabolism*
Neuronal Outgrowth / physiology*
Nogo Proteins / metabolism*
Protein Binding
Proteoglycans / metabolism
Receptors, Lysosphingolipid / metabolism

Substances

Carrier Proteins
Heparan Sulfate Proteoglycans
Nogo Proteins
Proteoglycans
Receptors, Lysosphingolipid
Heparitin Sulfate

Abstract

Publication types

MeSH terms

Substances

Grants and funding