The precise assembly of a functional nervous system relies on axon guidance cues. Beyond engaging their cognate receptors and initiating signaling cascades that modulate cytoskeletal dynamics, guidance cues also bind components of the extracellular matrix, notably proteoglycans, yet the role and mechanisms of these interactions remain poorly understood. We found that Drosophila secreted semaphorins bind specifically to glycosaminoglycan (GAG) chains of proteoglycans, showing a preference based on the degree of sulfation. Structural analysis of Sema2b unveiled multiple GAG-binding sites positioned outside canonical plexin-binding site, with the highest affinity binding site located at the C-terminal tail, characterized by a lysine-rich helical arrangement that appears to be conserved across secreted semaphorins. In vivo studies revealed a crucial role of the Sema2b C-terminal tail in specifying the trajectory of olfactory receptor neurons. We propose that secreted semaphorins tether to the cell surface through interactions with GAG chains of proteoglycans, facilitating their presentation to cognate receptors on passing axons.

• Klíčová slova
• Sema2b, axon guidance, glycosaminoglycans, semaphorin, semaphorin bridge model,
• MeSH
• axony metabolismus   MeSH
• čichové buňky metabolismus   MeSH
• Drosophila melanogaster metabolismus   MeSH
• glykosaminoglykany metabolismus   MeSH
• navádění axonů * MeSH
• proteiny Drosophily * metabolismus   genetika   MeSH
• proteoglykany * metabolismus   MeSH
• semaforiny * metabolismus   genetika   MeSH
• signální transdukce * MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glykosaminoglykany MeSH
• proteiny Drosophily * MeSH
• proteoglykany * MeSH
• semaforiny * MeSH