UBR-1 ubiquitin ligase regulates the balance between GABAergic and glutamatergic signaling.
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| Abstract |
Excitation/inhibition (E/I) balance is carefully maintained by the nervous system. The neurotransmitter GABA has been reported to be co-released with its sole precursor, the neurotransmitter glutamate. The genetic and circuitry mechanisms to establish the balance between GABAergic and glutamatergic signaling have not been fully elucidated. Caenorhabditis elegans DVB is an excitatory GABAergic motoneuron that drives the expulsion step in the defecation motor program. We show here that in addition to UNC-47, the vesicular GABA transporter, DVB also expresses EAT-4, a vesicular glutamate transporter. UBR-1, a conserved ubiquitin ligase, regulates DVB activity by suppressing a bidirectional inhibitory glutamate signaling. Loss of UBR-1 impairs DVB Ca2+ activity and expulsion frequency. These impairments are fully compensated by the knockdown of EAT-4 in DVB. Further, glutamate-gated chloride channels GLC-3 and GLC-2/4 receive DVB's glutamate signals to inhibit DVB and enteric muscle activity, respectively. These results implicate an intrinsic cellular mechanism that promotes the inherent asymmetric neural activity. We propose that elevated glutamate in ubr-1 mutants, being the cause of the E/I shift, potentially contributes to Johanson Blizzard syndrome.
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| Authors | Yi Li, Jyothsna Chitturi, Bin Yu, Yongning Zhang, Jing Wu, Panpan Ti, Wesley Hung, Mei Zhen, Shangbang Gao |
| Journal | EMBO reports (EMBO Rep) Vol. 24 Issue 11 Pg. e57014 (11 06 2023) ISSN: 1469-3178 [Electronic] England |
| PMID | 37811674 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
| Copyright | © 2023 The Authors. |
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