Histamine functions as a key neurotransmitter in multiple ci

Histamine functions as a key neurotransmitter in multiple circuits to control various behaviors. In Drosophila photoreceptor, TCS 5861528 is produced de novo by histidine decarboxylase (Burg et al., 1993); meanwhile, maintaining normal histamine content also depends on the histamine recycling pathway (Borycz et al., 2002, Chaturvedi et al., 2016, Stenesen et al., 2015, Xu et al., 2015). In both pathways, loading histamine into synaptic vesicles is critical for histaminergic neurotransmission (Figure 4). The absence of VMAT in some histaminergic neurons, including fly photoreceptors, suggests the existence of VMAT-independent vesicular transport of histamine. Here, we found a putative vesicular histamine transporter LOVIT in photoreceptor synaptic vesicles, providing the first evidence that a vesicular monoamine transporter other than VMAT protein may exist. It is speculated that other species may use a similar transporter to regulate the location of monoamines.
STAR★Methods
Acknowledgments We thank Dr. Janusz Borycz for helping with the experiments and for helpful suggestions and discussions. We are indebted to Dr. Ian A. Meinertzhagen for many helpful discussions and comments on the manuscript. We thank the Bloomington Stock Center, Tsinghua Fly Center, Vienna Drosophila Resource Center, Dr. C. Montell and S. Carroll, and the Developmental Studies Hybridoma Bank for reagents. We thank the Imaging Center at the Institute of Biophysics, Chinese Academy of Sciences, for EM section observations. We also thank the National Protein Science Facility at Tsinghua University and the Antibody Center at NIBS for technical assistance. This work was supported by a grant from the National Natural Science Foundation of China (81670891) and by a “973” grant (2014CB849700) from the Chinese Ministry of Science awarded to T.W. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Introduction Aquatic embryos, such as those of zebrafish (Danio rerio), rely upon cellular defenses to survive in challenging environments. In adult vertebrates, protective proteins are often expressed at environmental barrier tissues such as the gut, kidney, liver, and blood-brain barrier. In contrast, in the embryo, the internal detoxification organs are not yet mature, and the barrier function of detoxification organs is often carried out by cells at the embryo-environment interface (Epel et al., 2008). Zebrafish embryos have a specialized epidermis composed of five cell types: club cells, mucous cells, keratinocytes, ionocytes, and undifferentiated cells (Chang and Hwang, 2011). Upon completion of gastrulation, the zebrafish embryonic epidermis acts as the major barrier to accumulation of harmful small molecules into the embryo. Of the five epidermal cell types in the zebrafish embryo, only keratinocytes, mucous cells and ionocytes are directly exposed to the external environment. Ionocytes play an active role in the interaction of the embryo with its environment by maintaining osmotic homeostasis through active trans-epithelial ion transport (Hwang and Chou, 2013). These mitochondrion-rich cells become differentiated by 24 h post-fertilization (hpf) and are scattered throughout the embryonic epidermis (Hwang and Chou, 2013; Jänicke et al., 2007; Kim et al., 2017; Dymowska et al., 2012; Hsiao et al., 2007). Ionocytes will become restricted to the gills upon development of functional gills post-embryonic development, but during embryonic stages, ionoregulation of the fish is achieved through epidermal ionocytes (Hwang and Chou, 2013). Zebrafish ionocytes have been demonstrated to share functional similarities with mammalian kidney cells (Chang and Hwang, 2011). The four types of ionocytes include K+-secreting (KS) cells, Na+/Cl− cotransporter-expressing (NCC) cells, Na+/K+-ATPase-rich (NaR) cells, and H+-ATPase-rich (HR) cells (Hwang and Chou, 2013). Although ionocyte subtypes do not directly correspond to renal cell subtypes, ion transport functions can be divided between ionocytes similarly to those between renal cells. For example, HR cells secrete H+ like intercalated cells (ICs) and absorb Na+ like proximal tubular (PT) cells (Lin et al., 2006; Purkerson and Schwartz, 2007; Horng et al., 2009; Wagner et al., 2009; Lee et al., 2011).