Golgi apparatus proteome deciphering in living cells enabled by aggregation-induced emission luminogen-mediated photocatalytic proximity labeling (AIE-PhoPL)

Abstract

Abstract As a central platform of proteins sorting and signal docking, in situ Golgi apparatus (GA) proteome mapping is critical for elucidating relevant biological events. However, chemical proteomic dissection of GA is poorly studied owing to the lack of efficient labeling methods. Herein, we described an aggregation-induced emission luminogen-mediated photocatalytic proximity labeling strategy (AIE-PhoPL) that allowed dynamic profiling of GA proteome with high spatiotemporal precision in a native context. With the GA-targeting photocatalyst based on aggregation-induced emission luminogen (AIEgen), the proteins were activated and labeled locally in Golgi with high efficiency under control of visible light, enabling spatiotemporally resolved modifying of histidine and tyrosine residues. Upon validation in living HeLa cells which determined a significant portion of Golgi-associated proteins with 78% specificity, we applied AIE-PhoPL to dynamic proteome mapping of brain metastatic lung cancer cells and revealed the underlying roles GA played in signal transduction and extracellular matrix organization during cancer metastasis. This work provides a powerful tool to break out the dilemma for chemical labeling of GA proteome in living cells and fuels the research on diversification of controllable chemical probes for subcellular proteome labeling.