BAC-mediated transgenic expression of fluorescent autophagic protein Beclin 1 reveals a role for Beclin 1 in lymphocyte development

被引：42

作者：

Arsov, I. ^{[1
,2
]}

Li, X. ^{[2
]}

Matthews, G. ^{[1
]}

Coradin, J. ^{[1
]}

Hartmann, B. ^{[2
]}

Simon, A. K. ^{[2
,3
]}

Sealfon, S. C. ^{[2
]}

Yue, Z. ^{[2
]}

机构：

[1] CUNY York Coll, Dept Biol, Jamaica, NY 11451 USA

[2] Mt Sinai Sch Med, Dept Neurol & Neurosci, New York, NY USA

[3] John Radcliffe Hosp, Nuffield Dept Clin Med, Weatherall Inst Mol Med, Oxford OX3 9DU, England

来源：

CELL DEATH AND DIFFERENTIATION | 2008年 / 15卷 / 09期

基金：

美国国家卫生研究院;

关键词：

beclin; 1; autophagy; T cell; B cell; apoptosis;

D O I：

10.1038/cdd.2008.59

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：

Beclin 1/Atg6 is an essential component of the evolutionary conserved PtdIns(3)-kinase (Vps34) protein complex that regulates macroautophagy (autophagy) in eukaryotic cells and also interacts with antiapoptotic Bcl-2 family members, Bcl-2, and Bcl-x(L). To elucidate the physiological function of Beclin 1, we generated transgenic mice producing a green fluorescent Beclin 1 protein (Beclin 1-GFP) under Beclin 1 endogenous regulation. The beclin 1-GFP transgene is functional because it completely rescues early embryonic lethality in beclin 1-deficient mice. The transgenic mice appear normal, with undetected change in basal autophagy levels in different tissues, despite the additional expression of functional Beclin 1-GFP. Staining of Beclin 1-GFP shows mostly diffuse cytoplasmic distribution in various tissues. Detailed analysis of the transgene expression by flow cytometry reveals a Bcl-2-like biphasic expression pattern in developing T and B cells, as well as differential regulation of expression in mature versus immature thymocytes following in vitro stimulation. Moreover, thymocytes expressing high Beclin 1-GFP levels appear increasingly sensitive to glucocorticoid-induced apoptosis in vitro. Our results, therefore, support a role for Beclin 1 in lymphocyte development involving cross talk between autophagy and apoptosis.

引用

页码：1385 / 1395

页数：11

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