Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157
Regulation of neuronal survival and morphology by the E3 ubiquitin ligase RNF157
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DOI：
10.1038/cdd.2014.163
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发表时间：
2015-04-01
影响因子：
12.4
通讯作者：
Stegmueller, J.
中科院分区：
文献类型：
--
作者：
Matz, A.;Lee, S-J;Stegmueller, J.
神经元健康对于大脑的长期完整性至关重要。在这项研究中，我们的特点是新的E3泛素连接酶环指蛋白157（RNF 157），它显示了在小鼠脑中占主导地位的表达。RNF 157是E3连接酶mahogunin ring finger-1的同源物，其先前已涉及海绵状神经变性。我们鉴定了RNF 157作为培养神经元中存活的调节剂，并确定RNF 157的连接酶活性对这一过程至关重要。我们还发现，独立于其连接酶活性，RNF 157调节树突的生长和维持。我们进一步鉴定了衔接蛋白APBB 1（淀粉样β前体蛋白结合，家族B，成员1或Fe 65）作为控制神经元存活的RNF 157的相互作用物和蛋白水解底物。在这里，Fe 65与其相互作用伴侣RNA结合蛋白SART 3（T细胞3或Tip 110识别的鳞状细胞癌抗原）一起的核定位对于触发细胞凋亡至关重要。总之，我们描述了E3连接酶RNF 157调节神经元发育的重要方面。
Neuronal health is essential for the long-term integrity of the brain. In this study, we characterized the novel E3 ubiquitin ligase ring finger protein 157 (RNF157), which displays a brain-dominant expression in mouse. RNF157 is a homolog of the E3 ligase mahogunin ring finger-1, which has been previously implicated in spongiform neurodegeneration. We identified RNF157 as a regulator of survival in cultured neurons and established that the ligase activity of RNF157 is crucial for this process. We also uncovered that independently of its ligase activity, RNF157 regulates dendrite growth and maintenance. We further identified the adaptor protein APBB1 (amyloid beta precursor protein-binding, family B, member 1 or Fe65) as an interactor and proteolytic substrate of RNF157 in the control of neuronal survival. Here, the nuclear localization of Fe65 together with its interaction partner RNA-binding protein SART3 (squamous cell carcinoma antigen recognized by T cells 3 or Tip110) is crucial to trigger apoptosis. In summary, we described that the E3 ligase RNF157 regulates important aspects of neuronal development.