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. Author manuscript; available in PMC: 2014 Dec 4.
Published in final edited form as: Nat Commun. 2014 Nov 11;5:5209. doi: 10.1038/ncomms6209

Figure 6. GAG-mediated inhibition of synaptic RPTPσ:TrkC interaction and function.

Figure 6

(a) SPR analysis of human RPTPσ Ig1–3 and RPTPσ Ig1–3 ΔK binding to immobilized mouse TrkC LRRIg1 in the presence of increasing concentrations of HS or heparin-dp10. For sensograms see Supplementary Fig. 10a,b. (b,c) Induced synapsin clustering in rat hippocampal neurons by COS-7 cells expressing TrkC TM or NGL-3 in the presence of heparin-dp10, heparinases (Heps) or mock control. Analysis of variance P<0.0001, *P<0.01 and **P<0.001 compared with TrkC TM mock, whereas NGL-3 heparin-dp10 or heparainase groups were not significantly different from NGL-3 mock by post hoc Bonferroni’s multiple comparison test, n =16–26 cells from two experiments. Scale bar, 10 μM. (d) Illustration of the partial overlap between GAG- and TrkC-binding sites on RPTPσ. Top panel: the RPTPσ:TrkC complex, rotated 180° around the y axis relative to Fig. 2b. Lower panel: sucrose octasulphate (SOS, grey/red) is modelled in the RPTPσ GAG-binding site, an equivalent location to that observed in the LAR:SOS co-crystal structure (which is homologous with RPTPσ, PDB ID: 2YD8). SOS (or GAG) binding can out-compete the TrkC interaction with RPTPσ.