Histamine synthesis and transport are coupled in axon terminals via a dual quality control system.
| Autor: | Peng L; College of Biological Sciences, China Agricultural University, Beijing, China., Wang T; College of Biological Sciences, China Agricultural University, Beijing, China. wangtao1006@nibs.ac.cn.; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 100084, China. wangtao1006@nibs.ac.cn.; National Institute of Biological Sciences, Beijing, 102206, China. wangtao1006@nibs.ac.cn. |
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| Jazyk: | angličtina |
| Zdroj: | The EMBO journal [EMBO J] 2024 Oct; Vol. 43 (20), pp. 4472-4491. Date of Electronic Publication: 2024 Sep 06. |
| DOI: | 10.1038/s44318-024-00223-0 |
| Abstrakt: | Monoamine neurotransmitters generated by de novo synthesis are rapidly transported and stored into synaptic vesicles at axon terminals. This transport is essential both for sustaining synaptic transmission and for limiting the toxic effects of monoamines. Here, synthesis of the monoamine histamine by histidine decarboxylase (HDC) and subsequent loading of histamine into synaptic vesicles are shown to be physically and functionally coupled within Drosophila photoreceptor terminals. This process requires HDC anchoring to synaptic vesicles via interactions with N-ethylmaleimide-sensitive fusion protein 1 (NSF1). Disassociating HDC from synaptic vesicles disrupts visual synaptic transmission and causes somatic accumulation of histamine, which leads to retinal degeneration. We further identified a proteasome degradation system mediated by the E3 ubiquitin ligase, purity of essence (POE), which clears mislocalized HDC from the soma, thus eliminating the cytotoxic effects of histamine. Taken together, our results reveal a dual mechanism for translocation and degradation of HDC that ensures restriction of histamine synthesis to axonal terminals and at the same time rapid loading into synaptic vesicles. This is crucial for sustaining neurotransmission and protecting against cytotoxic monoamines. (© 2024. The Author(s).) |
| Databáze: | MEDLINE |
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