Aizawa Hiroyuki, Hu Shu-Ching, Bobb Kathryn, Balakrishnan Karthik, Ince Gulayse, Gurevich Inga, Cowan Mitra, Ghosh Anirvan
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Science. 2004 Jan 9;303(5655):197-202. doi: 10.1126/science.1089845.
The lasting effects of neuronal activity on brain development involve calcium-dependent gene expression. Using a strategy called transactivator trap, we cloned a calcium-responsive transactivator called CREST (for calcium-responsive transactivator). CREST is a SYT-related nuclear protein that interacts with adenosine 3',5'-monophosphate (cAMP) response element-binding protein (CREB)-binding protein (CBP) and is expressed in the developing brain. Mice that have a targeted disruption of the crest gene are viable but display defects in cortical and hippocampal dendrite development. Cortical neurons from crest mutant mice are compromised in calcium-dependent dendritic growth. Thus, calcium activation of CREST-mediated transcription helps regulate neuronal morphogenesis.
神经元活动对大脑发育的持久影响涉及钙依赖性基因表达。我们采用一种称为反式激活陷阱的策略,克隆了一种钙反应性反式激活因子,称为CREST(钙反应性反式激活因子)。CREST是一种与突触结合蛋白相关的核蛋白,它与3',5'-环磷酸腺苷(cAMP)反应元件结合蛋白(CREB)-结合蛋白(CBP)相互作用,并在发育中的大脑中表达。具有靶向破坏crest基因的小鼠是可存活的,但在皮质和海马树突发育方面表现出缺陷。来自crest突变小鼠的皮质神经元在钙依赖性树突生长方面受损。因此,CREST介导的转录的钙激活有助于调节神经元形态发生。