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Fbxo45 Forms a Novel Ubiquitin Ligase Complex and Is Required for Neuronal Development

机译：Fbxo45形成新型泛素连接酶复合物，是神经元发育所必需的

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Fbxo45 is an F-box protein that is restricted to the nervous system. Unlike other F-box proteins, Fbxo45 was found not to form an SCF complex as a result of an amino acid substitution in the consensus sequence for Cul1 binding. Proteomics analysis revealed that Fbxo45 specifically associates with PAM (protein associated with Myc), a RING finger-type ubiquitin ligase. Mice deficient in Fbxo45 were generated and found to die soon after birth as a result of respiratory distress. Fbxo45?/? embryos show abnormal innervation of the diaphragm, impaired synapse formation at neuromuscular junctions, and aberrant development of axon fiber tracts in the brain. Similar defects are also observed in mice lacking Phr1 (mouse ortholog of PAM), suggesting that Fbxo45 and Phr1 function in the same pathway. In addition, neuronal migration was impaired in Fbxo45?/? mice. These results suggest that Fbxo45 forms a novel Fbxo45-PAM ubiquitin ligase complex that plays an important role in neural development.
机译：Fbxo45是一种F-box蛋白，仅限于神经系统。与其他F-box蛋白不同，发现Fbxo45不会形成SCF复合物，这是由于在共有序列中结合了Cul1而进行了氨基酸取代。蛋白质组学分析显示Fbxo45与PAM（与Myc相关的蛋白质）特异性结合，PAM是一种RING指型泛素连接酶。缺乏Fbxo45的小鼠产生并发现其出生后由于呼吸窘迫而死亡。 Fbxo45 ？ / 胚胎显示diaphragm肌异常支配，神经肌肉接头处突触形成受损以及异常发育在大脑中的轴突纤维束。在缺乏Phr1（小鼠PAM的直系同源物）的小鼠中也观察到了类似的缺陷，表明Fbxo45和Phr1在相同的途径中起作用。此外， Fbxo45 ？ / ？小鼠的神经元迁移受到损害。这些结果表明，Fbxo45形成一种新型的Fbxo45-PAM泛素连接酶复合物，在神经发育中起重要作用。

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