A conserved insect transcobalamin-like gene is associated with vitamin B12-related functions in the silkworm Bombyx mori.

Abstract

Vitamin B12 (VB12, 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 transcobalamin (TCN)-like proteins retain a conserved fold and a pocket compatible with cobalamin binding, although direct biochemical validation remains needed. Bmtcn expression 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 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.