Identifying Secreted Proteins by Non-canonical Amino Acid Tagging

Identification of proteins secreted by specific subpopulations of cells is an important step in studies of cell-cell interaction. Here we describe a method to tag, enrich and identify secreted proteins in a cell-selective manner. Labeling is restricted to the cells of interest by introducing a mutant methionyl-tRNA synthetase that charges tRNAMet with azidonorleucine, which can be tagged by click chemistry. Proteins made by cells that do not express the mutant synthetase are not labeled. Applications of this approach to the identification of secreted proteins will be discussed.