Protein-specific imaging of posttranslational modifications.

Protein posttranslational modifications (PTMs) modulate protein function, trafficking, and interactions. Many PTMs ubiquitously occurs on hundreds and thousands of proteins, which makes cellular imaging of the PTM state of a specific protein like looking for a needle in a haystack. A proximity-enabled strategy, which exploits the spatial proximity between the PTM and the modified protein, has emerged as a valuable tool for protein-specific imaging of PTMs in single cells and tissue sections. The protein and the PTM are dually labeled with two distinct tags, which enable the generation of the nanometer proximity-dependent fluorescent signals for visualization. Herein, we review recent advances in the methodological developments and the applications of the proximity-enabled protein-specific imaging in studying phosphorylation, glycosylation, and lipidation.