Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology
Developmental expression of the SRF co-activator MAL in brain: role in regulating dendritic morphology
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DOI：
10.1111/j.1471-4159.2006.03992.x
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发表时间：
2006-09-01
影响因子：
4.7
通讯作者：
Tabuchi, Akiko
中科院分区：
文献类型：
--
作者：
Shiota, Jun;Ishikawa, Mitsuru;Tabuchi, Akiko
发育和成熟神经元所表现出的树突形态的动态变化激发了人们对破译所涉及的信号通路的兴趣。最近的研究发现，巨核细胞急性白血病（MAL）是一种血清反应因子（SRF）共激活因子，是连接肌动蛋白细胞骨架变化与SRF介导的转录的信号通路的关键组成部分。为了帮助确定这一通路在调节树突形态中的作用，我们描述了MAL在发育和成年大脑中的表达模式，并研究了其在调节培养皮层神经元树突形态中的作用。在小鼠脑的组织学研究中，我们发现MAL在成年海马和大脑皮层的神经元中有明显的表达。MAL免疫染色显示该蛋白定位于神经元细胞体和根尖树突。在发育过程中，MAL表达增加发生在产后第二周。在原代培养的皮质神经元中，显性MAL阴性结构或MAL siRNA的表达减少了树突突起的数量，降低了srf介导的转录的基础水平。综上所述，这些发现表明MAL-SRF信号通路在调节树突形态中起着关键作用。
The dynamic changes in dendritic morphology displayed by developing and mature neurons have stimulated interest in deciphering the signaling pathways involved. Recent studies have identified megakaryocytic acute leukemia (MAL), a serum response factor (SRF) co-activator, as a key component of a signaling pathway linking changes in the actin cytoskeleton to SRF-mediated transcription. To help define the role of this pathway in regulating dendritic morphology, we have characterized the pattern of MAL expression in the developing and adult brain, and have examined its role in regulating dendritic morphology in cultured cortical neurons. In histological studies of mouse brain, we found prominent expression of MAL in neurons in adult hippocampus and cerebral cortex. MAL immunostaining revealed localization of this protein in neuronal cell bodies and apical dendrites. During development, an increase in MAL expression occurs during the second post-natal week. Expression of dominant negative MAL constructs or MAL siRNA in cortical neurons grown in primary culture reduces the number of dendritic processes and decreases the basal level of SRF-mediated transcription. Taken together, these findings indicate that the MAL-SRF signaling pathway plays a key role in regulating dendritic morphology.