Journal Article

DKFZ-2017-05182

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Control of Cell Shape, Neurite Outgrowth, and Migration by a Nogo-A/HSPG Interaction.

Kempf, A. ; Boda, E. ; Kwok, J. C. F. ; Fritz, R. ; Grande, V. ; Kaelin, A. M. ; Ristic, Z. ; Schmandke, A. ; Schmandke, A. ; Tews, B.DKFZ* ; Fawcett, J. W. ; Pertz, O. ; Buffo, A. ; Schwab, M. E.

2017
Cell Press Cambridge, Mass.

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Please use a persistent id in citations: 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.

Keyword(s): Carrier Proteins ; Heparan Sulfate Proteoglycans ; Nogo Proteins ; Proteoglycans ; Receptors, Lysosphingolipid ; Heparitin Sulfate

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Contributing Institute(s):

1. AG Molekulare Mechanismen der Tumorzell-Invasion (V077)

Research Program(s):

1. 319H - Addenda (POF3-319H) (POF3-319H)

Appears in the scientific report 2017

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Database coverage:
; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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