Liquid-liquid phase separation facilitates the biogenesis of secretory storage granules
| Autor: | Parchure, Anup, Tian, Meng, Stalder, Danièle, Boyer, Cierra K, Bearrows, Shelby C, Rohli, Kristen E, Zhang, Jianchao, Rivera-Molina, Felix, Ramazanov, Bulat R, Mahata, Sushil K, Wang, Yanzhuang, Stephens, Samuel B, Gershlick, David C, Von Blume, Julia |
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| Přispěvatelé: | Parchure, Anup [0000-0003-1452-799X], Tian, Meng [0000-0003-3665-5095], Stalder, Danièle [0000-0002-6996-4006], Boyer, Cierra K [0000-0003-1195-7169], Bearrows, Shelby C [0000-0001-7289-5673], Rohli, Kristen E [0000-0002-4805-111X], Zhang, Jianchao [0000-0002-3269-4639], Ramazanov, Bulat R [0000-0001-8335-3685], Wang, Yanzhuang [0000-0002-1864-7094], Gershlick, David C [0000-0002-0602-210X], von Blume, Julia [0000-0001-6665-1592], Apollo - University of Cambridge Repository |
| Rok vydání: | 2022 |
| Předmět: | |
| Popis: | Funder: Yale-start up grant Funder: NIGMS NIH HHS Funder: Fraternal Order of Eagles Diabetes Research Center Funder: Sir Henry Dale Funder: University of Iowa Funder: PI Daniel Eberl Funder: Royal Society210481 Insulin is synthesized by pancreatic β-cells and stored into secretory granules (SGs). SGs fuse with the plasma membrane in response to a stimulus and deliver insulin to the bloodstream. The mechanism of how proinsulin and its processing enzymes are sorted and targeted from the trans-Golgi network (TGN) to SGs remains mysterious. No cargo receptor for proinsulin has been identified. Here, we show that chromogranin (CG) proteins undergo liquid-liquid phase separation (LLPS) at a mildly acidic pH in the lumen of the TGN, and recruit clients like proinsulin to the condensates. Client selectivity is sequence-independent but based on the concentration of the client molecules in the TGN. We propose that the TGN provides the milieu for converting CGs into a "cargo sponge" leading to partitioning of client molecules, thus facilitating receptor-independent client sorting. These findings provide a new receptor-independent sorting model in β-cells and many other cell types and therefore represent an innovation in the field of membrane trafficking. |
| Databáze: | OpenAIRE |
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