Data from: The UBR-1 ubiquitin ligase regulates glutamate metabolism to generate coordinated motor pattern in C. elegans

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 synchronized motor neuron activation, preventing body bending when animals generate reversal movements. This motor deficit is rescued by removing GOT-1, a transaminase that converts aspartate to glutamate. Both UBR-1 and GOT-1 are critically required in premotor interneurons of the reverse 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.

UBR1是一种E3泛素连接酶（E3 ubiquitin ligase），其最广为人知的功能是通过N端规则（N-end rule）介导靶蛋白的降解。然而，UBR家族蛋白的生理功能仍未得到完全阐明。我们发现，秀丽隐杆线虫（C. elegans）UBR-1的功能缺失会引发运动神经元同步激活，导致线虫在产生后退运动时无法完成身体弯曲动作。该运动缺陷可通过敲除GOT-1得到恢复——GOT-1是一种可将天冬氨酸转化为谷氨酸的转氨酶（transaminase）。UBR-1与GOT-1均在后退运动环路的运动前中间神经元（premotor interneurons）中发挥关键调控作用，以调节运动模式。ubr-1与got-1突变体的谷氨酸水平分别呈现升高与降低的变化。上述研究结果提出了一个引人关注的推测：UBR家族蛋白可参与调控谷氨酸代谢。