Evolution of mannose 6-phosphate receptors (MPR300 and 46): lysosomal enzyme sorting proteins.
Lysosomal enzymes undergo phosphorylation on their mannose residues in the Golgi apparatus and are recognized by two distinct type I transmembrane glycoproteins designated as the mannose 6-phosphate receptors; MPR300, (Mr 300 kDa) and MPR46, (Mr 46 kDa) that internally transport them to the lysosomes. In humans, absence of this recognition system leads to severe lysosomal storage disease, emphasizing their essential role in the biogenesis of lysosomes. Among the two receptors only MPR46 shows an absolute requirement for divalent metal ions. Only MPR300 is known to be a multifunctional protein that also binds many other ligands such as the human IGF-II, thyroglobulin, retinoic acid, granzyme A and B. In mammals, the extracytoplasmic domain of MPR300 protein is comprised of 15 repetitive cassettes which share significant similarity with each other and also with the single cassette that constitutes the extracytoplasmic domain of MPR46. Therefore it became necessary to understand the evolution of these receptors. Homologous proteins were affinity purified from different non-mammalian vertebrates such as birds, reptiles, amphibians, fish and also from the invertebrates, echinodermates (starfish) and molluscs (unio). Cloning and sequencing of both receptors from different mammals, chicken, fish and MPR46 from starfish revealed that these proteins exhibit similar structural domains as the mammalian receptors. alpha-fucosidase characterized from the molluscs exhibits specific interaction with the putative MPR300 protein from the same species. Available evidence suggests evolutionary conservation of both receptors from molluscs, as below these species no receptors that bind phosphomannan have been identified.
Nadimpalli
S K
SK
Department of Biochemistry, University of Hyderabad, India. drnsk7@yahoo.co.in
Amancha
P K
PK
D000818:Animals; D006801:Humans; D008247:Lysosomes / Q000201:enzymology* / Q000378:metabolism*; D008970:Molecular Weight; D017527:Receptor, IGF Type 2 / Q000737:chemistry / Q000378:metabolism*; D005644:alpha-L-Fucosidase / Q000378:metabolism
D017527:Receptor, IGF Type 2; D005644:alpha-L-Fucosidase