Fujishima Kazuto, Kiyonari Hiroshi, Kurisu Junko, Hirano Tomoo, Kengaku Mineko
Laboratory for Neural Cell Polarity, RIKEN Brain Science Institute, Saitama, Japan.
J Neurochem. 2007 Jul;102(1):77-92. doi: 10.1111/j.1471-4159.2007.04478.x.
The septins constitute a family of GTPase proteins that are involved in many cytological processes such as cytokinesis and exocytosis. Previous studies have indicated that mammalian Sept3 is a brain-specific protein that is abundant in synaptic terminals. Here, we further investigated the localization and function of Sept3 in the mouse brain. Sept3 is expressed in several types of post-mitotic neurons, including granule cells in the cerebellum and pyramidal neurons in the cerebral cortex and hippocampus. In primary cultures of hippocampal pyramidal neurons, Sept3 protein is enriched at the tips of growing neurites during differentiation. Sept3 directly binds to Sept5 and Sept7 and forms a heteromeric complex at nerve terminals adjacent to where a synaptic vesicle marker, synaptophysin, is expressed in mature neurons. When over-expressed in HEK293 cells, Sept3 forms filamentous structures that are dependent on the presence of its GTP- and phosphoinositide-binding domains. To investigate the physiological roles of Sept3, we generated Sept3 deficient mice. These mice show no apparent abnormalities in histogenesis nor neuronal differentiation in culture. Expression of synaptic proteins and other septins are unaltered, indicating that Sept3 is dispensable for normal neuronal development.
Septins构成了一个GTPase蛋白家族，参与许多细胞学过程，如胞质分裂和胞吐作用。先前的研究表明，哺乳动物的Sept3是一种在大脑中特异性表达的蛋白，在突触终末中含量丰富。在此，我们进一步研究了Sept3在小鼠大脑中的定位和功能。Sept3在几种有丝分裂后的神经元中表达，包括小脑颗粒细胞、大脑皮层和海马体中的锥体神经元。在海马锥体神经元的原代培养中，Sept3蛋白在分化过程中富集于生长中的神经突尖端。Sept3直接与Sept5和Sept7结合，并在与成熟神经元中突触囊泡标记物突触素表达相邻的神经末梢形成异源复合物。当在HEK293细胞中过表达时，Sept3形成丝状结构，这依赖于其GTP和磷酸肌醇结合结构域的存在。为了研究Sept3的生理作用，我们构建了Sept3基因敲除小鼠。这些小鼠在组织发生或培养中的神经元分化方面没有明显异常。突触蛋白和其他Septins的表达未改变，表明Sept3对于正常神经元发育并非必需。
