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The Septin CDCrel-1 Is Dispensable for Normal Development and Neurotransmitter Release

机译:Septin CDCrel-1可用于正常发育和神经递质释放

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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.
机译:Septins是在多种生物中完成胞质分裂所需的GTPases,但在此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septin CDCrel-1主要在神经系统(主要是有丝分裂后的组织)中表达。尽管对该蛋白的功能知之甚少,但我们先前已证明它与调节分泌有关。此外,编码该蛋白的基因定位到在心-心面部和DiGeorge综合征中经常缺失的基因座,最近已证明CDCrel-1是帕金E3泛素连接酶活性的直接靶标,帕金森是常染色体隐性遗传的病因帕金森氏病的各种形式。在这里,我们显示CDCrel-1表达在突触成熟时升高,并且CDCrel-1存在于复合物中,包括Septins Nedd5和CDC10。为了研究其在神经系统中的功能,我们生成了纯合的CDCrel-1空小鼠,并显示这些小鼠在体外突触特性和海马神经元生长方面看来是正常的。此外,我们发现,虽然CDCrel-1突变小鼠中许多突触蛋白的表达不受影响,但其他septins的表达却发生了改变。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表达的变化可能是其功能冗余的原因。

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