Abstract
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.
Highlights
In eukaryotic cells, the ubiquitin-proteasome system mediates selective protein degradation [1, 2]
We found that the C. elegans UBR-1 regulates glutamate level
When UBR-1 is defective, C. elegans exhibits increased glutamate; this leads to synchronization of motor neuron
Summary
The ubiquitin-proteasome system mediates selective protein degradation [1, 2]. Restoring UBR-1 expression by either Pglr-1 or Pnmr-1 significantly rescued ubr-1 mutants’ motor defects, including bending, duration, and frequency during reversal movements (Fig 2C; S3A and S3B Fig), whereas restoring UBR-1 in motor neurons did not (Fig 2C; S3A and S3B Fig). Both Pglr-1 and Pnmr-1 activate expression in premotor interneurons of the reversal motor circuit, AVA, AVE, AVD, and RIM [28,29,30]. UBR-1’s role in the reversal motor circuit involves the whole network of premotor interneurons, with AVA, AVE, and maybe RIM being the most critical components
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