Novel chemical tool for understanding membrane remodelling in the cell

What is it about?

Membranes of cells are highly dynamic mosaic-fluid structures that undergo constant reshaping. A group of proteins, the Endosomal Sorting Complex Required for Transport (ESCRT), plays a crucial role in membrane remodelling - a cellular process involving the rearrangement of cellular membranes. Understanding and controlling specific parts of ESCRT is challenging due to its complex organization. Here we describe a natural product-like compound Tantalosin that specifically disrupts a particular part of ESCRT called the IST1-CHMP1B complex. Tantalosin is a synthetic molecule inspired by alkaloids from the medical plant Cinchona. Using Tantalosin as a chemical tool, we examine how this complex contributes to different membrane remodelling events. Interestingly, Tantalosin induces non-canonical LC3 lipidation - a process involving non-canonical autophagy (self-eating) - at stalled endosomes. This discovery further enriches our understanding of ESCRT function and highlights the importance of novel small molecules as valuable tools for unravelling complex biological mechanisms.

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Photo by ANIRUDH on Unsplash

Photo by ANIRUDH on Unsplash

Why is it important?

The findings lead to a deeper understanding of how an evolutionary successful programme of membrane remodelling works in human cells and future development of new drugs.

Perspectives