Journal Article

Cycling molecular assemblies for Golgi imaging and disruption

Lau, William, Hong, Pengyu, Dinulescu, Daniela, Gerton, Thomas, Dresselhaus, Erica C., Xu, Bing, Zhang, Qiuxin, Copperman, Noah, Lu, Lei, Liu, Zhiyu, Mahajan, Divyanshu, Xia, Chaoshuang, Qiu, Kangqiang, Lee, Mikki, Hsieh, Jer-Tsong, Loeb, David M., Tan, Weiyi, Lin, Cheng, Ashton-Rickardt, Isabela, Rodal, Avital A., Drapkin, Ronny, Diao, Jiajie

2026

Overview

The Golgi apparatus is a central hub for protein trafficking and signaling, yet its rapid imaging and cell-selective disruption remain challenging. Here, we report cycling molecular assemblies (CyMA) for fast Golgi imaging and cell-selective interference. CyMA precursors are acetylated amphiphilic thiopeptides that traverse plasma membrane and are deacetylated by intracellular thioesterases. This exposes thiols that undergo palmitoylation by Golgi-resident palmitoyl acyltransferases utilizing palmitoyl-CoA. The resulting palmitoylated peptides self-assemble into dynamic nanostructures (i.e., CyMA) localized at the Golgi. Their continuous, reversible S -acylation enables near-instantaneous Golgi imaging. Replacing fluorophore with a biphenyl motif promotes CyMA accumulation and disrupts functions such as protein modifications, trafficking, and secretion, leading to cell death. This study establishes dynamic supramolecular assembly as an active and selective strategy for Golgi-targeting, pleiotropically interfering with Golgi functions, which may be applicable to targeting other organelles by utilizing alternative enzyme switches to enable kinetic trapping. Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14/1 / 14/19 / 14/28 / 14/34 / 14/35 / 14/63 / 38/109 / 38/89 / 631/80/2373 / 631/92/611 / 639/638/541/966 / 82/51 / 82/58 / Acylation / Animals / Assemblies / Cancer / Cell death / Cell growth / Cell Membrane - metabolism / Cycles / Disruption / Enzymes / Glycosylation / Golgi Apparatus - metabolism / Golgi Apparatus - ultrastructure / Golgi cells / Growth factors / HeLa Cells / Humanities and Social Sciences / Humans / Imaging / Kinases / Lipoylation / Metastasis / multidisciplinary / Nanostructure / Organelles / Palmitoylation / Peptides / Peptides - chemistry / Peptides - metabolism / Protein Transport / Proteins / Science / Science (multidisciplinary) / Thiols