裂殖酵母SAGA复合物亚基Spt20参与钙调蛋白磷酸酶调节的Cl-胞内平衡

doi:10.3724/SP.J.1005.2013.01135

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HEREDITAS ›› 2013, Vol. 35 ›› Issue (9): 1135-1142.doi: 10.3724/SP.J.1005.2013.01135

SAGA complex subunit Spt20 involves in the calcineurin-mediated Cl- homeostasis in Schizosaccharomyces pombe

ZHOU Nan, LEI Bing-Kun, ZHOU Xing, YU Yao, LV Hong

State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China

Received:2013-04-06 Revised:2013-05-16 Online:2013-09-20 Published:2013-09-25

Abstract

Abstract:

SAGA (Spt-Ada-Gcn5 acetyltransferase) is a highly conserved protein complex in eukaryotes, which plays a role in many important cellular processes, including transcriptional activation and mRNA exportation. In order to investigate the potential biological function of SAGA subunit, we performed a yeast two-hybrid screen using a core structural subunit of SAGA in fission yeast, Spt20, as the bait. Ppb1, catalytic subunit of calcineruin was identified in the test. Calcineurin is a key regulator of signal transduction. The interaction between Spt20 and Ppb1 was confirmed by yeast two-hybrid assay and co-immunoprecipitation. In S. pombe, ppb1Δ was hypersensitive to high concentration of Cl?. In contrast, spt20Δ could resist high concentration of Cl?, which maintained normal growth of cells. Fluorescent colocalization analysis showed that Ppb1 was translocated from cytoplasm to nucleus and colocalized with Spt20 upon the increase of extracellular Cl?. Further genetic analysis revealed that loss of spt20+ suppressed the hypersensitive phenotype to Cl? of ppb1Δ. Thus, spt20+ and ppb1+ stayed in the same pathway of regulating Cl? homeostasis and spt20+ functioned downstream of ppb1+. Our data suggest that spt20Δ is able to resist high concentration of extracellular Cl? and Spt20 involves in the calcineurin-mediated Cl? homeostasis. The aberrant up-regulation of intracellular Cl? is correlated with the diseases like myocardial ischemia reperfusion injury in higher organism. As Spt20 is highly conserved in eukaryotes, it might serve as a potential drug target in Cl? imbalance related diseases.

Key words: SAGA complex, Spt20, calcineurin, Cl?homeostasis, S. pombe

ZHOU Nan LEI Bing-Kun ZHOU Xing YU Yao LV Hong. SAGA complex subunit Spt20 involves in the calcineurin-mediated Cl- homeostasis in Schizosaccharomyces pombe[J]. HEREDITAS, 2013, 35(9): 1135-1142.

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SAGA complex subunit Spt20 involves in the calcineurin-mediated Cl- homeostasis in Schizosaccharomyces pombe

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