Vitamin B12 (cobalamin) is delivered by transcobalamin-dependent pathways in mammals, but comparable host-encoded factors and functions in insects remain unclear. Here we identify a single transcobalamin-like gene in the silkworm Bombyx mori (Bmtcn) and detect homologs across diverse insect orders. Structure prediction and docking suggest that insect TCN-like proteins retain a conserved fold and a pocket compatible with cobalamin binding, although direct biochemical validation remains needed. Bmtcn is enriched in the head and is detectable across neuronal and glial populations, implicating the nervous system as a potential site of cobalamin handling and/or demand. Bmtcn Loss-of-function mutants accumulate homocysteine, display behavioral abnormalities, and show brain-associated phenotypes. Head transcriptomics reveals coordinated changes consistent with perturbed folate–one-carbon metabolism and broad remodeling of core cellular programs alongside stress-associated responses in the mutants. Because insects lack the canonical cobalamin-dependent methionine synthase, these findings suggest that cobalamin may act through alternative metabolic and/or signaling routes. Together, our results implicate a conserved insect transcobalamin-like component in vitamin B12–linked physiology and B. mori as a tractable system for mechanistic dissection.
Jiahao et al. (Thu,) studied this question.