Your browser doesn't support javascript.
loading
Rab27a negatively regulates phagocytosis by prolongation of the actin-coating stage around phagosomes.
Yokoyama, Kunio; Kaji, Hiroaki; He, Jinsong; Tanaka, Chisato; Hazama, Ryoichi; Kamigaki, Takashi; Ku, Yonson; Tohyama, Kaoru; Tohyama, Yumi.
  • Yokoyama K; Division of Gastroenterological Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
J Biol Chem ; 286(7): 5375-82, 2011 Feb 18.
Article en En | MEDLINE | ID: mdl-21169636
ABSTRACT
Rab27a, a Rab family small GTPase, is involved in the exocytosis of secretory granules in melanocytes and cytotoxic T-cells. Rab27a mutations cause type 2 Griscelli syndrome, which is characterized by immunodeficiency, including uncontrolled macrophage activation known as hemophagocytic syndrome. However, the role of Rab27a in phagocytosis remains elusive. Here, using macrophage-like differentiated HL-60 cells and C3bi-opsonized zymosan as a pathogen-phagocyte model, we show that Rab27a negatively regulates complement-mediated phagocytic activity in association with F-actin remodeling. We found that transfection of Rab27a shRNA into HL-60 cells enhances complement-mediated phagocytosis. To clarify the mechanisms underlying the elevated phagocytosis in Rab27a knockdown cells, we analyzed the process of phagosome formation focusing on F-actin dynamics F-actin assembly, followed by F-actin extension around the particles and the subsequent degradation of F-actin, leading to internalization of the particles enclosed in phagosomes. Microscopic analysis revealed that these actin-related processes, including F-actin coating and F-actin degradation, proceed more rapidly in Rab27a knockdown cells than in control HL-60 cells. Both elevated phagocytosis and accelerated F-actin remodeling were restored by expression of rescue-Rab27a and Rab27a-Q78L (GTP-bound form), but not by Rab27a-T23N (GDP-bound form). Furthermore, an increased accumulation of Coronin 1A surrounding F-actin coats was observed in Rab27a knockdown cells, suggesting that the function of Coronin 1A is related to the regulation of the F-actin coating. Our findings demonstrate that Rab27a plays a direct regulatory role in the nascent process of phagocytosis by prolongation of the stage of actin coating via suppression of Coronin 1A. This study may contribute to an explanation of the underlying mechanisms of excessive phagocytosis observed in Griscelli syndrome.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fagocitosis / Fagosomas / Actinas / Proteínas de Unión al GTP rab / Macrófagos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2011 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Fagocitosis / Fagosomas / Actinas / Proteínas de Unión al GTP rab / Macrófagos Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Año: 2011 Tipo del documento: Article