The septin CDCrel-1 is dispensable for normal development and neurotransmitter release
The septin CDCrel-1 is dispensable for normal development and neurotransmitter release
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DOI：
10.1128/mcb.22.1.378-387.2002
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发表时间：
2002-01-01
影响因子：
5.3
通讯作者：
Trimble, WS
中科院分区：
文献类型：
--
作者：
Peng, XR;Jia, ZP;Trimble, WS
在许多生物体中，胞质分裂是完成胞质分裂所需的GTP酶，但它们在这一过程中的作用尚不清楚。由于哺乳动物septin CDCrel-1主要在神经系统（主要是有丝分裂后组织）中表达，因此Septins可能具有额外的功能。虽然对这种蛋白质的功能知之甚少，但我们以前已经表明它参与调节分泌。此外，编码这种蛋白质的基因映射到在velo-cardiofacial和DiGeorge综合征中经常缺失的基因座，并且CDCrel-1最近已被证明是Parkin的E3泛素连接酶活性的直接靶标，Parkin是帕金森病的常染色体隐性形式的致病因子。在这里，我们表明，CDCrel-1的表达在突触成熟时上升，并且CDCrel-1存在于包括septins Nedd 5和CDC 10的复合物中。为了研究其在神经系统中的功能，我们产生了纯合子CDCrel-1 null小鼠，并表明这些小鼠在体外突触特性和海马神经元生长方面表现正常。此外，我们发现，虽然在CDCrel-1突变小鼠中许多突触蛋白的表达不受影响，但其他septins的表达发生了变化。总之，这些数据表明，CDCrel-1不是神经元发育或功能所必需的，其他septins表达的变化可能是其功能冗余的原因。
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.