Peng Xiao-Rong, Jia Zhengping, Zhang Yu, Ware Jerry, Trimble William S
Programmes in Cell Biology. Brain and Behavior, Hospital for Sick Children, Toronto, Ontario, Canada.
Mol Cell Biol. 2002 Jan;22(1):378-87. doi: 10.1128/MCB.22.1.378-387.2002.
Septins are GTPases required for the completion of cytokinesis in a variety of organisms, yet their role in this process is not known. Septins may have additional functions since the mammalian septin CDCrel-1 is predominantly expressed in the nervous system, a largely postmitotic tissue. While relatively little is known about the function of this protein, we have previously shown that it is involved in regulated secretion. In addition, the gene encoding this protein maps to a locus often deleted in velo-cardiofacial and DiGeorge syndromes, and CDCrel-1 has recently been shown to be a direct target of the E3 ubiquitin ligase activity of Parkin, a causative agent in autosomal recessive forms of Parkinson's disease. Here we show that CDCrel-1 expression rises at the time of synaptic maturation and that CDCrel-1 is present in a complex that includes the septins Nedd5 and CDC10. To investigate its function in the nervous system, we generated homozygotic CDCrel-1 null mice and showed that these mice appear normal with respect to synaptic properties and hippocampal neuron growth in vitro. Moreover, we found that while the expression of a number of synaptic proteins is not affected in the CDCrel-1 mutant mice, the expression of other septins is altered. Together, these data suggest that CDCrel-1 is not essential for neuronal development or function, and that changes in expression of other septins may account for its functional redundancy.
Septins是多种生物体中细胞分裂完成所必需的GTP酶,但其在这一过程中的作用尚不清楚。Septins可能具有其他功能,因为哺乳动物的septin CDCrel-1主要在神经系统中表达,而神经系统在很大程度上是有丝分裂后的组织。虽然对这种蛋白质的功能了解相对较少,但我们之前已经表明它参与了调节性分泌。此外,编码这种蛋白质的基因定位于一个在心脏-颜面和迪格奥尔格综合征中经常缺失的位点,最近有研究表明CDCrel-1是帕金森病常染色体隐性形式的致病因子Parkin的E3泛素连接酶活性的直接靶点。在这里,我们表明CDCrel-1的表达在突触成熟时升高,并且CDCrel-1存在于一个包含septins Nedd5和CDC10的复合物中。为了研究其在神经系统中的功能,我们构建了纯合的CDCrel-1基因敲除小鼠,并表明这些小鼠在突触特性和体外海马神经元生长方面看起来正常。此外,我们发现虽然一些突触蛋白的表达在CDCrel-1突变小鼠中不受影响,但其他septins的表达发生了改变。总之,这些数据表明CDCrel-1对于神经元发育或功能不是必需的,其他septins表达的变化可能解释了其功能冗余。