Lysosomal enzyme sorting receptors-where did they first appear in the animal kingdom?

Abstract

Two distinct but homologous mannose 6-phosphate receptors (MPRs) designated as the cation-independent mannose 6-phosphate/IGF-II receptor (MPR300, Mr 300 kDa) and the cation-dependent mannose 6-phosphate receptor (MPR46, Mr 46 kDa) are evolutionarily conserved proteins that transport lysosomal enzymes to lysosomes in the vertebrates. MPR300 alone has also been shown to be an endocytic receptor and it also binds human IGF-II. To further understand the evolution of the MPRs, we extended our studies to the invertebrate species by initially identifying one of their interacting partners, such as α-fucosidase. In the highly evolved invertebrate, starfish (echinodermata) and unio (mollusca) lysosomal enzyme activities were detected and an α-fucosidase has been affinity purified. Additionally, both putative receptors were also affinity purified from these species. In Biomphalaria glabrata (snail cells), the MPR300 protein has been shown to be involved in lysosomal enzyme targeting. Below the molluscs, in the Drosophila melanogaster we could discover only a truncated form of the MPR300 protein which lacks the ability to bind multivalent phosphomannan like the other known receptors. No MPR 46 protein was detected in this species. Furthermore, in species such as the prawn (arthropoda) and the earthworm (annelidae), that fall below the mollusca only MPR 300-like polypeptides were detectable and no MPR 46 protein was identified. In comparison to molluscs, the lysosomal activities detectable were in the order arthropoda greater than annelidae. Our data strongly suggests that the functional MPRs started appearing in the animal kingdom from the mollusc onwards © 2012 Springer Science+Business Media, LLC.