Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
PLoS Genet. 2018 Apr 12;14(4):e1007303. doi: 10.1371/journal.pgen.1007303. eCollection 2018 Apr.
UBR1 is an E3 ubiquitin ligase best known for its ability to target protein degradation by the N-end rule. The physiological functions of UBR family proteins, however, remain not fully understood. We found that the functional loss of C. elegans UBR-1 leads to a specific motor deficit: when adult animals generate reversal movements, A-class motor neurons exhibit synchronized activation, preventing body bending. This motor deficit is rescued by removing GOT-1, a transaminase that converts aspartate to glutamate. Both UBR-1 and GOT-1 are expressed and critically required in premotor interneurons of the reversal motor circuit to regulate the motor pattern. ubr-1 and got-1 mutants exhibit elevated and decreased glutamate level, respectively. These results raise an intriguing possibility that UBR proteins regulate glutamate metabolism, which is critical for neuronal development and signaling.
UBR1 是一种 E3 泛素连接酶，其以靶向 N 端规则的蛋白质降解的能力而闻名。然而，UBR 家族蛋白的生理功能仍未完全了解。我们发现，秀丽隐杆线虫 UBR-1 的功能丧失会导致特定的运动缺陷：当成年动物产生反转运动时，A 类运动神经元表现出同步激活，从而阻止身体弯曲。这种运动缺陷可以通过去除 GOT-1（一种将天冬氨酸转化为谷氨酸的转氨酶）得到挽救。UBR-1 和 GOT-1 都在反转运动回路的中间神经元中表达，并对其运动模式的调节至关重要。ubr-1 和 got-1 突变体分别表现出谷氨酸水平升高和降低。这些结果提出了一个有趣的可能性，即 UBR 蛋白调节谷氨酸代谢，这对神经元发育和信号传递至关重要。
