Ocadaic acid treatment causes tyrosine phosphorylation of caveolin-2 and induces internalization of caveolae in rat peritoneal macrophages

被引:16
作者
Kiss, AL
Botos, E
Turi, A
Müllner, N
机构
[1] Semmelweis Univ, Dept Human Morphol & Dev Biol, H-1450 Budapest, Hungary
[2] Semmelweis Univ, Dept Med Chem Mol & Pathobiochem, H-1085 Budapest, Hungary
关键词
caveolae-cycle; tyrosine phosphorylation; caveolin-2; resident and elicited macrophages; phosphatase inhibitors;
D O I
10.1016/j.micron.2004.04.003
中图分类号
TH742 [显微镜];
学科分类号
摘要
In this paper. we provide evidences that protein phosphatases could regulate the internalization cycle of caveolae in rat peritoneal cells. Ocadaic acid (OA)-a serine/threonine phosphatase inhibitor-was used in various concentrations (4 and 100 nM) to study the internalization of horseradish peroxidase (HRP) in resident and elicited macrophages. We have found that OA in both concentrations has significantly decreased HRP uptake in resident and elicited cells. The results of our morphometrical analysis showed that in OA-treated cells, the number of surface-connected caveolae has been dramatically decreased. Simultaneously large, endosome-like, vacuoles containing small vesicles appeared in the cytoplasm. The membrane of these small vesicles was labeled with anti-caveolin-1 antibody. Immunoprecipitation and Western blot analysis revealed that in OA-treated cells a similar to29 kDa protein identified as caveolin-2 in macrophages was phosphorylated on tyrosine residues. These data support the idea that there is a close correlation between the phosphorylation of caveolin-2 and endocytosis of caveolae: the tyrosine phosphorylation of this similar to29 kDa protein can drive caveolae to pinch off from the plasma membrane and causes accumulation of caveolae in a multivesicular body-like cellular compartment, which was never found to contain lysosomal enzymes. As a result of OA treatment caveolin-2 remains phosphorylated and the phosphorylation of these protein might inhibit the recycling of caveolae. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:707 / 715
页数:9
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