在小脑颗粒神经元凋亡开始时，THG-1pit转移至细胞核。

THG-1pit moves to nucleus at the onset of cerebellar granule neurons apoptosis.

作者信息

Canterini Sonia, Bosco Adriana, De Matteis Valentina, Mangia Franco, Fiorenza Maria Teresa

机构信息

Department of Psychology, Section of Neuroscience, Istituto Pasteur-Fondazione Cenci Bolognetti and "Daniel Bovet" Research Center, La Sapienza University of Rome, Italy.

出版信息

Mol Cell Neurosci. 2009 Feb;40(2):249-57. doi: 10.1016/j.mcn.2008.10.013. Epub 2008 Nov 19.

DOI:10.1016/j.mcn.2008.10.013

PMID:19084601

Abstract

Thg-1pit (Tsc22d4), a murine gene belonging to the TGF-beta1-stimulated clone 22 domain (TSC22D) family, is expressed in developing and adult cerebellar granule neurons and mature Purkinje cells. We have studied THG-1pit function in primary cultures of mouse cerebellar granule neurons maintained in vitro in the presence of a medium containing 25 mM K+ (differentiating condition) or 5 mM K+ (pro-apoptotic condition), and determined the effect of culture medium, TGF-beta1 and IGF-1 on THG-1pit expression and intracellular localization. Thg-1pit encoded a 42 kDa MW protein and other, higher MW and developmentally-regulated forms. Cell exposure to 5 mM K+ elicited early and/or late waves of Thg-1pit transcription, depending on the presence/absence of TGF-beta1, and caused THG-1pit to massively and transiently move from cytoplasm and neurites to the nucleus. THG-1pit nuclear entrance was concomitant to that of AIF, suggesting that THG-1pit is involved in the induction of granule neuron apoptosis.

摘要

Thg-1pit（Tsc22d4）是一种属于转化生长因子β1刺激克隆22结构域（TSC22D）家族的小鼠基因，在发育中的和成年的小脑颗粒神经元以及成熟的浦肯野细胞中表达。我们研究了在含有25 mM K⁺（分化条件）或5 mM K⁺（促凋亡条件）的培养基存在下体外培养的小鼠小脑颗粒神经元原代培养物中Thg-1pit的功能，并确定了培养基、转化生长因子β1和胰岛素样生长因子-1对Thg-1pit表达和细胞内定位的影响。Thg-1pit编码一种分子量为42 kDa的蛋白质以及其他分子量更高且受发育调节的形式。细胞暴露于5 mM K⁺会引发Thg-1pit转录的早期和/或晚期波动，这取决于转化生长因子β1的存在与否，并导致THG-1pit从细胞质和神经突大量且短暂地转移到细胞核。THG-1pit进入细胞核与凋亡诱导因子（AIF）同时发生，这表明THG-1pit参与了颗粒神经元凋亡的诱导。