Abstract
Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present. In Caenorhabditis elegans, axon regeneration is regulated by DDR-2, a receptor tyrosine kinase (RTK) that contains a discoidin domain and modulates the Met-like SVH-2 RTK–JNK MAP kinase signaling pathway. Here, we describe the svh-10/sqv-3 and svh-11 genes, which encode components of a conserved glycosylation pathway, and show that they modulate axon regeneration in C. elegans. Overexpression of svh-2, but not of ddr-2, can suppress the axon regeneration defect observed in svh-11 mutants, suggesting that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway. Furthermore, we found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect. These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans.
Highlights
Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present
The svh-9 gene is identical to the nstp-1 gene, which is homologous to the human solute carrier transporter 35 B4 gene (SLC35B4), encoding a Golgi apparatus-localized nucleotide sugar transporter with dual specificity for UDP-xylose (UDP-Xyl) and UDP-N-acetylglucosamine (UDP-GlcNAc) (Figure 1B, Figure S1A, and Figure S2)
discoidin domain receptor (DDR)-2::GFP was detected with Aspergillus oryzae lectin (AOL) in svh-11(km86); ddr-2(tm797) mutants (Figure 5C). These results suggest that SVH-11 has no apparent effect on the DDR-2 fucosylation and that the other fucosyltransferases in C. elegans may be responsible for the modification
Summary
Axon regeneration following neuronal injury is an important repair mechanism that is not well understood at present. We found that DDR-2 is N-glycosylated at the Asn-141 residue located in its discoidin domain, and mutation of this residue caused an axon regeneration defect These findings indicate that N-linked glycosylation plays an important role in axon regeneration in C. elegans. We investigate the roles of SVH-10 and SVH11 in regulating axon regeneration These two gene products are involved in protein glycosylation, and genetic analysis suggests that SVH-11 functions between DDR-2 and SVH-2 in this glycosylation pathway. We show that DDR-2 is N-glycosylated at Asn-141 in its extracellular domain and that loss of N-glycosylation at this site decreases the signaling capability of DDR-2 in axon regeneration These results indicate that N-linked glycosylation plays an important role in the control of C. elegans axon regeneration
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