Tadr is an axonal histidine transporter required for visual neurotransmission in Drosophila.

Yongchao Han,Lei Peng,Tao Wang

doi:10.7554/elife.75821

Yongchao Han, Lei Peng + Show 1 more

Open Access

https://doi.org/10.7554/elife.75821

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Journal: eLife	Publication Date: Mar 1, 2022
Citations: 5	License type: CC BY 4.0

Affiliation: National Institute of Biological Sciences, Beijing

Abstract

Neurotransmitters are generated by de novo synthesis and are essential for sustained, high-frequency synaptic transmission. Histamine, a monoamine neurotransmitter, is synthesized through decarboxylation of histidine by histidine decarboxylase (Hdc). However, little is known about how histidine is presented to Hdc as a precursor. Here, we identified a specific histidine transporter, TADR (torn and diminished rhabdomeres), which is required for visual transmission in Drosophila. Both TADR and Hdc localized to neuronal terminals, and mutations in tadr reduced levels of histamine, thus disrupting visual synaptic transmission and phototaxis behavior. These results demonstrate that a specific amino acid transporter provides precursors for monoamine neurotransmitters, providing the first genetic evidence that a histidine amino acid transporter plays a critical role in synaptic transmission. These results suggest that TADR-dependent local de novo synthesis of histamine is required for synaptic transmission.

Highlights

Deficiencies in the biosynthesis of monoamine neurotransmitter such as dopamine contribute to a range of neurological disorders, such as dystonic and parkinsonian syndromes (Kurian et al, 2011)
In support of this hypothesis, we found that Histidine decarboxylase (Hdc) localized exclusively to photoreceptor terminals
In Drosophila photoreceptor cells, histamine is initially synthesized from histidine by the eye-specific enzyme, histidine decarboxylase (Hdc)

Summary

Introduction

Deficiencies in the biosynthesis of monoamine neurotransmitter such as dopamine contribute to a range of neurological disorders, such as dystonic and parkinsonian syndromes (Kurian et al, 2011). Both TADR and Hdc localized to neuronal terminals, and mutations in tadr reduced levels of histamine, disrupting visual synaptic transmission and phototaxis behavior. TADR localized predominantly to photoreceptor terminals and transported the amino acid histidine.

Results

Conclusion