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Sci Rep. 2017 Apr 21;7:46569. doi: 10.1038/srep46569.

Fatty acid synthase cooperates with protrudin to facilitate membrane outgrowth of cellular protrusions.

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State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.


Cellular protrusion formation capacity is a key feature of developing neurons and many eukaryotic cells. However, the mechanisms underlying membrane growth in protrusion formation are largely unclear. In this study, photo-reactive unnatural amino acid 3-(3-methyl-3H-diazirin-3-yl)-propamino-carbonyl-Nε-l-lysine was incorporated by a genetic code expansion strategy into protrudin, a protein localized in acidic endosomes and in the endoplasmic reticulum, that induces cellular protrusion and neurite formation. The modified protrudin was used for covalent trapping of protrudin-interacting proteins in living cells. Fatty acid synthase (FASN), which synthesizes free fatty acids, was identified to transiently interact with protrudin. Further characterization revealed a unique cooperation mechanism in which protrudin cooperates with FASN to facilitate cellular protrusion formation. This work reveals a novel mechanism involved in protrusion formation that is dependent on transient interaction between FASN and protrudin, and establishes a creative strategy to investigate transient protein-protein interactions in mammalian cells.

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