Intracellular Ca2+ and Zn2+ levels regulate the alternative cell density-dependent secretion of S100B in human glioblastoma cells

被引:85
作者
Davey, GE [1 ]
Murmann, P [1 ]
Heizmann, CW [1 ]
机构
[1] Univ Zurich, Dept Pediat, Div Clin Chem & Biochem, CH-8032 Zurich, Switzerland
关键词
D O I
10.1074/jbc.M103541200
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
In recent years, protein translocation has been implicated as the mechanism that controls assembly of signaling complexes and induction of signaling cascades. Several members of the multifunctional Ca2+ (Zn2+ - and Cu2+)-binding S100 proteins appear to translocate upon cellular stimulation, and some are even secreted from cells, exerting extracellular functions. We transfected cells with S100B-green fluorescent fusion proteins and followed the relocation in real time. A small number of cells underwent translocation spontaneously. However, the addition of thapsigargin, which increases Ca2+ levels, intensified ongoing translocation and secretion or induced these processes in resting cells. On the other hand, EGTA or BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N ' ,N ' -tetraacetic acid), the Ca2+-chelating agents, inhibited these processes. In contrast, relocation of S100B seemed to be negatively dependent on Zn2+ levels. Treatment of cells with TPEN (NNN ' ,N ' -tetrakis(2-pyridylmethyl)ethylenediamine), a Zn2+-binding drug, resulted in a dramatic redistribution and translocation of S100B. Secretion of S100B, when measured by ELISA, was dependent on cell density. As cells reached confluence the secretion drastically declined. However, an increase in Ca2+ levels, and even more so, a decrease in Zn2+ concentration, reactivated secretion of S100B. On the other hand, secretion did not decrease by treatment with brefeldin A, supporting the view that this process is independent of the endoplasmic reticulum-Golgi classical secretion pathway.
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页码:30819 / 30826
页数:8
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