| Autor: |
Rui Santalla Méndez, Andrea Rodgers Furones, René Classens, Manon Haverdil, Marta Canela Capdevila, Anne van Duffelen, Cornelia G. Spruijt, Michiel Vermeulen, Martin ter Beest, Annemiek B. van Spriel, Laia Querol Cano |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.05.13.491792 |
| Popis: |
Intracellular vesicle transport is essential for cellular homeostasis and is partially mediated by SNARE proteins. Endosomal trafficking to the plasma membrane ensures cytokine secretion in dendritic cells (DCs) and the initiation of immune responses. Despite its critical importance, the specific molecular agents that regulate DC cytokine secretion are poorly characterised. Galectin-9, a ß-galactoside-binding protein, has emerged as a novel cellular modulator although its exact intracellular roles in regulating (immune) cell homeostasis and vesicle transport are virtually unknown. We investigated galectin-9 function in primary human DCs and report that galectin-9 is essential for intracellular cytokine trafficking to the cell surface. Galectin-9-depleted DCs accumulate cytokine-containing vesicles in the Golgi complex that eventually undergo lysosomal degradation. We observed galectin-9 to molecularly interact with Vamp-3 using immunoprecipitation-mass-spectrometry and identified galectin-9 was required for rerouting Vamp-3-containing endosomes upon DC activation as the underlying mechanism. Overall, this study identifies galectin-9 as a necessary mechanistic component for intracellular trafficking. This may impact our general understanding of vesicle transport and shed new light into the multiple roles galectins play in governing cell function. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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