Spatially targeted chemokine exocytosis guides transmigration at lymphatic endothelial multicellular junctions.
EMBO J
; 43(15): 3141-3174, 2024 Aug.
Article
en En
| MEDLINE
| ID: mdl-38877304
ABSTRACT
Migrating cells preferentially breach and integrate epithelial and endothelial monolayers at multicellular vertices. These sites are amenable to forces produced by the migrating cell and subsequent opening of the junctions. However, the cues that guide migrating cells to these entry portals, and eventually drive the transmigration process, are poorly understood. Here, we show that lymphatic endothelium multicellular junctions are the preferred sites of dendritic cell transmigration in both primary cell co-cultures and in mouse dermal explants. Dendritic cell guidance to multicellular junctions was dependent on the dendritic cell receptor CCR7, whose ligand, lymphatic endothelial chemokine CCL21, was exocytosed at multicellular junctions. Characterization of lymphatic endothelial secretory routes indicated Golgi-derived RAB6+ vesicles and RAB3+/27+ dense core secretory granules as intracellular CCL21 storage vesicles. Of these, RAB6+ vesicles trafficked CCL21 to the multicellular junctions, which were enriched with RAB6 docking factor ELKS (ERC1). Importantly, inhibition of RAB6 vesicle exocytosis attenuated dendritic cell transmigration. These data exemplify how spatially-restricted exocytosis of guidance cues helps to determine where dendritic cells transmigrate.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Proteínas de Unión al GTP rab
/
Exocitosis
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Quimiocina CCL21
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Receptores CCR7
Límite:
Animals
/
Humans
Idioma:
En
Revista:
EMBO J
Año:
2024
Tipo del documento:
Article
País de afiliación:
Finlandia
Pais de publicación:
Reino Unido