Golgi apparatus-associated secretome deciphering in living cells enabled by aggregation-induced emission luminogen-mediated photocatalytic proximity labeling

ABSTRACT: Secretome is intimately linked to Golgi apparatus (GA) which acts as a transition platform of proteins processing and sorting in trafficking pathways. GA-associated secretome runs through the endomembrane system and is critical for inter- and intracellular communication networks. However, achieving in situ dissection of GA-associated secretome remains challenging 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-associated secretome with high spatiotemporal precision in minutes. With the GA-targeting photocatalyst based on aggregation-induced emission luminogen (AIEgen), the proteins were labeled locally in Golgi lumen with high efficiency under light, enabling spatiotemporally resolved modifying of histidine and tyrosine residues. AIE-PhoPL strategy was successfully utilized in living HeLa and hard-to-transfect macrophage HMC3 cells by determining a significant subset of GA-associated secretome with 80% specificity, linking the distinct GA-associated secretory profiles to cellular characteristics. We further applied AIE-PhoPL to dynamic proteome mapping of brain and bone metastatic lung cancer cells, which revealed GA-associated secretory proteomic patterns related to metastatic mechanisms and the underlying roles GA-associated secretion played in extracellular matrix organization during metastasis. This work provides a powerful tool to break out the dilemma for chemical labeling of GA-associated secretome in living cells and fuels the research on diversification of controllable chemical probes for subcellular proteome labeling.

ORGANISM(S): Homo Sapiens

SUBMITTER: Lihua Zhang  

PROVIDER: PXD066788 | iProX | Wed Jul 30 00:00:00 BST 2025

REPOSITORIES: iProX