Brito de Souza Lorena, Pinto da Silva Luis Lamberti, Jamur Maria Célia, Oliver Constance
Department of Cell and Molecular Biology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
PLoS One. 2014 Mar 11;9(3):e91868. doi: 10.1371/journal.pone.0091868. eCollection 2014.
Phospholipase D (PLD) has been implicated in many cellular functions, such as vesicle trafficking, exocytosis, differentiation, and proliferation. The aim of this study was to characterize the role of PLD in HSY cells, a human cell line originating from the intercalated duct of the parotid gland. As the function and intracellular localization of PLD varies according to cell type, initially, the intracellular localization of PLD1 and PLD2 was determined. By immunofluorescence, PLD1 and PLD2 both showed a punctate cytoplasmic distribution with extensive co-localization with TGN-46. PLD1 was also found in the nucleus, while PLD2 was associated with the plasma membrane. Treatment of cells with the primary alcohol 1-butanol inhibits the hydrolysis of phosphatidylcoline by PLD thereby suppressing phosphatidic acid (PA) production. In untreated HSY cells, there was only a slight co-localization of PLD with the clathrin coated vesicles. When HSY cells were incubated with 1-butanol the total number of clathrin coated vesicles increased, especially in the juxtanuclear region and the co-localization of PLD with the clathrin coated vesicles was augmented. Transmission electron microscopy confirmed that the number of Golgi-associated coated vesicles was greater. Treatment with 1-butanol also affected the Golgi apparatus, increasing the volume of the Golgi saccules. The decrease in PA levels after treatment with 1-butanol likewise resulted in an accumulation of enlarged lysosomes in the perinuclear region. Therefore, in HSY cells PLD appears to be involved in the formation of Golgi associated clathrin coated vesicles as well as in the structural maintenance of the Golgi apparatus.
磷脂酶D(PLD)参与了许多细胞功能,如囊泡运输、胞吐作用、分化和增殖。本研究的目的是确定PLD在HSY细胞中的作用,HSY细胞是一种源自腮腺闰管的人类细胞系。由于PLD的功能和细胞内定位因细胞类型而异,因此首先确定了PLD1和PLD2的细胞内定位。通过免疫荧光法,PLD1和PLD2均显示出点状的细胞质分布,并与TGN-46广泛共定位。还发现PLD1存在于细胞核中,而PLD2与质膜相关。用伯醇1-丁醇处理细胞可抑制PLD对磷脂酰胆碱的水解,从而抑制磷脂酸(PA)的产生。在未处理的HSY细胞中,PLD与网格蛋白包被囊泡仅有轻微的共定位。当HSY细胞与1-丁醇孵育时,网格蛋白包被囊泡的总数增加,尤其是在近核区域,并且PLD与网格蛋白包被囊泡的共定位增强。透射电子显微镜证实,与高尔基体相关的包被囊泡数量更多。用1-丁醇处理也影响了高尔基体,增加了高尔基体囊泡的体积。用1-丁醇处理后PA水平的降低同样导致核周区域中扩大的溶酶体积累。因此,在HSY细胞中,PLD似乎参与了与高尔基体相关的网格蛋白包被囊泡的形成以及高尔基体的结构维持。