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

Kempf, Anissa; Boda, Enrica; Kwok, Jessica C F; Fritz, Rafael; Grande, Valentina; Kaelin, Andrea M; Ristic, Zorica; Schmandke, Andre; Schmandke, Antonio; Tews, Bjoern; Fawcett, James W; Pertz, Olivier; Buffo, Annalisa; Schwab, Martin E (2017). Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction. Developmental cell, 43(1), 24-34.e5. Cell Press 10.1016/j.devcel.2017.08.014

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

UniBE Contributor:

Pertz, Olivier

Subjects:

500 Science > 570 Life sciences; biology
500 Science

ISSN:

1534-5807

Publisher:

Cell Press

Language:

English

Submitter:

Olivier Pertz

Date Deposited:

19 Feb 2018 15:28

Last Modified:

26 Oct 2019 08:50

Publisher DOI:

10.1016/j.devcel.2017.08.014

PubMed ID:

28943240

Uncontrolled Keywords:

HSPG RMS SVZ adhesion migration neuroblast nogo-A outgrowth spreading syndecan

BORIS DOI:

10.7892/boris.109215

URI:

https://boris.unibe.ch/id/eprint/109215

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