Tsuchiya Daiju, Kitamura Yoshihisa, Takata Kazuyuki, Sugisaki Tatsuhiko, Taniguchi Takashi, Uemura Kengo, Miki Hiroaki, Takenawa Tadaomi, Shimohama Shun
Department of Neurobiology, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan.
Neurosci Res. 2006 Dec;56(4):459-69. doi: 10.1016/j.neures.2006.09.007. Epub 2006 Oct 16.
The actin cytoskeleton plays a critical role in the cellular morphological changes. Its organization is essential for neurite extension and synaptogenesis under the processes of neuronal development. Recently, neural Wiskott-Aldrich syndrome protein (N-WASP) and WASP family verprolin-homologous protein (WAVE) have been identified as key molecules, which specifically participate in regulation of actin cytoskeleton through small GTPases. The functions of these factors have been investigated using cultured cells; however, in vivo developmental changes in these factors are not fully understood. In this study, we examined the expression levels and distributions of N-WASP, WAVE and their related proteins in the rat cerebral cortex and hippocampus during postnatal development. Protein levels of these factors were progressively increased during development, and actin was accumulated in membranous fractions. Immunoreactivities for these factors were widely but differentially observed in entire brain. In the developing brain, N-WASP and WAVE seemed to exist in the synapse-rich areas, such as stratum radiatum of hippocampal CA1 subfield. A similar tendency in the distributions of these factors was observed in the mature brain. Taken together, N-WASP, WAVE and their related proteins may participate in normal brain development and synaptic plasticity by regulating the actin cytoskeleton.
肌动蛋白细胞骨架在细胞形态变化中起关键作用。其组织对于神经元发育过程中的神经突延伸和突触形成至关重要。最近,神经威斯科特-奥尔德里奇综合征蛋白(N-WASP)和WASP家族维普洛林同源蛋白(WAVE)已被确定为关键分子,它们通过小GTP酶特异性参与肌动蛋白细胞骨架的调节。这些因子的功能已在培养细胞中进行了研究;然而,这些因子在体内的发育变化尚未完全了解。在本研究中,我们检测了出生后发育过程中大鼠大脑皮层和海马中N-WASP、WAVE及其相关蛋白的表达水平和分布。这些因子的蛋白水平在发育过程中逐渐增加,并且肌动蛋白在膜组分中积累。在整个大脑中广泛但不同程度地观察到这些因子的免疫反应性。在发育中的大脑中,N-WASP和WAVE似乎存在于富含突触的区域,如海马CA1亚区的辐射层。在成熟大脑中也观察到这些因子分布的类似趋势。综上所述,N-WASP、WAVE及其相关蛋白可能通过调节肌动蛋白细胞骨架参与正常的大脑发育和突触可塑性。