Distal tip cell migration mutants of Caenorhabditis elegans are rescued by bioequivalent outputs from chondroitin and N-glycosylation pathways

秀丽隐杆线虫远端细胞迁移突变体可通过软骨素和N-糖基化途径的生物等效产物得到挽救。

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Abstract

In Caenorhabditis elegans, gonadal morphogenesis begins with the post-embryonic birth of two distal tip cells (DTCs) that migrate in phase 1 along the ventral body-wall in opposite directions. Phase 2 comprises a 90(°) turn followed by migration in a dorsal direction. Here, we identify a genetic dependency between two glycosylation pathways that modify proteins at different sites and display bioequivalence that ensures phase 2 navigation at elevated temperatures. Loss-of-function (lf) mutations in one putative and one proven β4N-acetylgalactosaminyltransferase:- ngat-1(null) predicted to affect the formation of LacdiNAc on complex-type N-glycans and mig-22(lf) affecting chondroitin synthesis, each disrupted phase 2 with incomplete penetrance, whereas ngat-1;mig-22 double mutant was disrupted with high penetrance (>90%). Single mutants were rescued by a 1- to 2-day starvation-induced larval diapause (protective developmental arrest) followed by refeeding (S/R), but ngat-1;mig-22 was not rescued, suggesting the two gene products function redundantly. GlcNAc supplementation to the hexosamine biosynthesis pathway (HBP), or gain-of-function mig-22(k185gf) rescued ngat-1(null), consistent with a compensating redundancy driven by enhanced UDP-HexNAc flux. Our results suggest that β-galactosides, structural features common to chondroitin and glycoproteins, contribute robustness that ensures DTC phase 2 fidelity under stressful thermal and nutritional conditions.

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