Cell-type-specific labeling and profiling of glycans in living mice.
Nat Chem Biol
; 18(6): 625-633, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35513511
ABSTRACT
Metabolic labeling of glycans with clickable unnatural sugars has enabled glycan analysis in multicellular systems. However, cell-type-specific labeling of glycans in vivo remains challenging. Here we develop genetically encoded metabolic glycan labeling (GeMGL), a cell-type-specific strategy based on a bump-and-hole pair of an unnatural sugar and its matching engineered enzyme. N-pentynylacetylglucosamine (GlcNAl) serves as a bumped analog of N-acetylglucosamine (GlcNAc) that is specifically incorporated into glycans of cells expressing a UDP-GlcNAc pyrophosphorylase mutant, AGX2F383G. GeMGL with the 1,3-di-O-propionylated GlcNAl (1,3-Pr2GlcNAl) and AGX2F383G pair was demonstrated in cell cocultures, and used for specific labeling of glycans in mouse xenograft tumors. By generating a transgenic mouse line with AGX2F383G expressed under a cardiomyocyte-specific promoter, we performed specific imaging of cardiomyocyte glycans in the heart and identified 582 cardiomyocyte O-GlcNAcylated proteins with no interference from other cardiac cell types. GeMGL will facilitate cell-type-specific glycan imaging and glycoproteomics in various tissues and disease models.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos
/
Acetilglucosamina
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article