Targeted disruption of Sept3, a heteromeric assembly partner of Sept5 and Sept7 in axons, has no effect on developing CNS neurons
Targeted disruption of Sept3, a heteromeric assembly partner of Sept5 and Sept7 in axons, has no effect on developing CNS neurons
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DOI：
10.1111/j.1471-4159.2007.04478.x
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发表时间：
2007-07-01
影响因子：
4.7
通讯作者：
Kengaku, Mineko
中科院分区：
文献类型：
--
作者：
Fujishima, Kazuto;Kiyonari, Hiroshi;Kengaku, Mineko
脓蛋白构成 GTP 酶蛋白家族，参与许多细胞学过程，例如胞质分裂和胞吐作用。先前的研究表明，哺乳动物 Sept3 是一种大脑特异性蛋白质，在突触末梢中含量丰富。在这里，我们进一步研究了 Sept3 在小鼠大脑中的定位和功能。 Sept3 在多种类型的有丝分裂后神经元中表达，包括小脑中的颗粒细胞以及大脑皮层和海马中的锥体神经元。在海马锥体神经元的原代培养物中，Sept3 蛋白在分化过程中生长的神经突尖端处富集。 Sept3 直接与 Sept5 和 Sept7 结合，并在神经末梢形成异聚复合物，该神经末梢邻近成熟神经元中表达突触小泡标记物突触素的位置。当在 HEK293 细胞中过表达时，Sept3 形成丝状结构，该结构依赖于其 GTP 和磷酸肌醇结合域的存在。为了研究 Sept3 的生理作用，我们培育了 Sept3 缺陷小鼠。这些小鼠在培养物中没有表现出组织发生和神经元分化的明显异常。突触蛋白和其他 septin 的表达未改变，表明 Sept3 对于正常神经元发育是可有可无的。
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.