Frontiers in immunology · 2025
P-Rex1 controls phagocytosis and the killing of bacteria by murine neutrophils independently of its catalytic activity.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Islam Priota, Chu Julia Y, Chetwynd Stephen A, Walker Rachael, Hawkins Phillip T, Welch Heidi C E
Аннотация
INTRODUCTION: P-Rex1 is a guanine-nucleotide factor for the small GTPase Rac (Rac-GEF) that is known to mediate neutrophil migration and ROS production in response to the activation of GPCRs. These roles of P-Rex1 are assumed to require its activation of Rac.
METHODS: Here, we used mice which lack P-Rex1 (Prex1 -/-) and mice with catalytically inactive P-Rex1 (Prex1GD ) to investigate the importance of the Rac-GEF activity in migration and ROS production. We also studied the requirement for P-Rex1 in degranulation, phagocytosis, NET formation, and the bactericidal activity of neutrophils.
RESULTS: We show that P-Rex1 mediates migration, ROS, and NETs through its Rac-GEF activity, but is dispensable for the degranulation of azurophil, specific and gelatinase granules. Surprisingly, P-Rex1 mediates the clearance of bacteria in vivo during septic peritonitis and the killing of bacteria by isolated neutrophils independently of its catalytic Rac-GEF activity. P-Rex1 also mediates the phagocytosis of IgG-opsonized zymosan yeast particles independently of its catalytic Rac-GEF activity. P-Rex1 is required for both integrin-dependent and Fc receptor-dependent phagocytosis, and it mediates the Fc receptor-dependent activation of Rac and Syk. Recently identified adaptor functions of P-Rex1 in GPCR trafficking and glucose uptake do not seem to underlie its GEF-activity independent roles in neutrophils.
DISCUSSION: Together, our study identifies P-Rex1 as a regulator of NET formation and phagocytosis in neutrophils and reveals that P-Rex1 mediates bactericidal activity and phagocytosis independently of its catalytic Rac-GEF activity, through mechanisms not obviously linked to other recently identified adaptor functions.
METHODS: Here, we used mice which lack P-Rex1 (Prex1 -/-) and mice with catalytically inactive P-Rex1 (Prex1GD ) to investigate the importance of the Rac-GEF activity in migration and ROS production. We also studied the requirement for P-Rex1 in degranulation, phagocytosis, NET formation, and the bactericidal activity of neutrophils.
RESULTS: We show that P-Rex1 mediates migration, ROS, and NETs through its Rac-GEF activity, but is dispensable for the degranulation of azurophil, specific and gelatinase granules. Surprisingly, P-Rex1 mediates the clearance of bacteria in vivo during septic peritonitis and the killing of bacteria by isolated neutrophils independently of its catalytic Rac-GEF activity. P-Rex1 also mediates the phagocytosis of IgG-opsonized zymosan yeast particles independently of its catalytic Rac-GEF activity. P-Rex1 is required for both integrin-dependent and Fc receptor-dependent phagocytosis, and it mediates the Fc receptor-dependent activation of Rac and Syk. Recently identified adaptor functions of P-Rex1 in GPCR trafficking and glucose uptake do not seem to underlie its GEF-activity independent roles in neutrophils.
DISCUSSION: Together, our study identifies P-Rex1 as a regulator of NET formation and phagocytosis in neutrophils and reveals that P-Rex1 mediates bactericidal activity and phagocytosis independently of its catalytic Rac-GEF activity, through mechanisms not obviously linked to other recently identified adaptor functions.