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The glycan-binding properties of the cation-independent mannose 6-phosphate receptor are evolutionary conserved in vertebrates. Glycobiology 2012 Jul;22(7):983-96

Date

03/01/2012

Pubmed ID

22369936

Pubmed Central ID

PMC3355666

DOI

10.1093/glycob/cws058

Scopus ID

2-s2.0-84861409583 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

The 300-kDa cation-independent mannose 6-phosphate receptor (CI-MPR) plays an essential role in the biogenesis of lysosomes by delivering newly synthesized lysosomal enzymes from the trans Golgi network to the endosomal system. The CI-MPR is expressed in most eukaryotes, with Saccharomyces cerevisiae and Caenorhabditis elegans being notable exceptions. Although the repertoire of glycans recognized by the bovine receptor has been studied extensively, little is known concerning the ligand-binding properties of the CI-MPR from non-mammalian species. To assess the evolutionary conservation of the CI-MPR, surface plasmon resonance analyses using lysosomal enzymes with defined N-glycans were carried out to probe the glycan-binding specificity of the Danio rerio CI-MPR. The results demonstrate that the D. rerio CI-MPR harbors three glycan-binding sites that, like the bovine CI-MPR, map to domains 3, 5 and 9 of its 15-domain-containing extracytoplasmic region. Analyses on a phosphorylated glycan microarray further demonstrated the unique binding properties of each of the three sites and showed that, similar to the bovine CI-MPR, only domain 5 of the D. rerio CI-MPR is capable of recognizing Man-P-GlcNAc-containing glycans.

Author List

Castonguay AC, Lasanajak Y, Song X, Olson LJ, Cummings RD, Smith DF, Dahms NM

Authors

Nancy M. Dahms PhD Professor in the Biochemistry department at Medical College of Wisconsin
Linda J. Olson PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Binding Sites
Binding, Competitive
Carbohydrate Conformation
Carbohydrate Sequence
Cells, Cultured
Cellulases
Conserved Sequence
Evolution, Molecular
Humans
Immobilized Proteins
Molecular Sequence Data
Polysaccharides
Protein Array Analysis
Protein Binding
Protein Structure, Tertiary
Receptor, IGF Type 2
Sugar Phosphates
Surface Plasmon Resonance
Vertebrates
Zebrafish
Zebrafish Proteins
alpha-Glucosidases