Low molecular weight group IIA and group V phospholipase A2 enzymes have different intracellular locations in mouse bone marrow-derived mast cells

被引:55
作者
Bingham, CO
Fijneman, RJA
Friend, DS
Goddeau, RP
Rogers, RA
Austen, KF
Arm, JP
机构
[1] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA
[4] Brigham & Womens Hosp, Partners Asthma Ctr, Boston, MA 02115 USA
[5] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Biomed Imaging Lab, Boston, MA 02115 USA
关键词
D O I
10.1074/jbc.274.44.31476
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The subcellular location of the enzymes of eicosanoid biosynthesis is critical for their co-ordinate action in the generation of leukotrienes and prostaglandins. This activity is thought to occur predominantly at a perinuclear location. Whereas the subcellular locations of cytosolic phospholipase (PL) A(2) and each of the pathway enzymes of eicosanoid generation have been defined, the distribution of the low molecular weight species of PLA(2) has remained elusive because of the lack of antibodies that distinguish among homologous family members. We have prepared affinity-purified rabbit antipeptide IgG antibodies that distinguish mouse group IIA PLA(2) and group V PLA(2). Immunofluorescence staining and immunogold electron microscopy reveal different subcellular locations for the enzymes. Group IIA(2) PLA(2) is present in the secretory granules of mouse bone marrow-derived mast cells, consistent with its putative role in facilitating secretory granule exocytosis and its consequent extracellular action. In contrast, group V PLA(2) is associated with various membranous organelles including the Golgi apparatus, nuclear envelope, and plasma membrane. The perinuclear location of group V PLA(2) is consistent with a putative interaction with translocated cytosolic PLA(2) in supplying arachidonic acid for generation of eicosanoid products, while the location in Golgi cisternae may also reflect its action as a secreted enzyme. The spatial segregation of group IIA PLA(2) and group V PLA(2) implies that these enzymes are not functionally redundant.
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页码:31476 / 31484
页数:9
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