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Sci Rep
2023 Mar 17;131:4416. doi: 10.1038/s41598-023-31503-0.
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Hiat1 as a new transporter involved in ammonia regulation.
Fehsenfeld S
,
Quijada-Rodriguez AR
,
Zhouyao H
,
Durant AC
,
Donini A
,
Sachs M
,
Eck P
,
Weihrauch D
.
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The orphan transporter hippocampus-abundant transcript 1 (Hiat1) was first identified in the mammalian brain. Its specific substrate specificity, however, has not been investigated to date. Here, we identified and analyzed Hiat1 in a crustacean, the green crab Carcinus maenas. Our phylogenetic analysis showed that Hiat1 protein is conserved at a considerable level between mammals and this invertebrate (ca. 78% identical and conserved amino acids). Functional expression of Carcinus maenas Hiat1 in Xenopus laevis oocytes demonstrated the capability to transport ammonia (likely NH4+) in a sodium-dependent manner. Furthermore, applying quantitative polymerase chain reaction, our results indicated a physiological role for Carcinus maenas Hiat1 in ammonia homeostasis, as mRNA abundance increased in posterior gills in response to elevated circulating hemolymph ammonia upon exposure to high environmental ammonia. Its ubiquitous mRNA expression pattern also suggests an essential role in general cellular detoxification of ammonia. Overall, our results introduce a new ubiquitously expressed ammonia transporter, consequently demanding revision of our understanding of ammonia handling in key model systems from mammalian kidneys to crustacean and fish gills.
Figure 3. Flux studies in Xenopus laevis oocytes expressing Carcinus maenas Hiat1. (A) Absolute H3-methylamine/ammonium (MA/MA+) uptake of sham-injected oocytes (white bar) and oocytes expressing Carcinus maenas Hiat1 (dark grey bar) under control conditions (medium pH 7.5, bath [total MA/MA+] = 1 mmol = 10 μCi). (B) Net changes in MA/MA+ uptake (calculated as [Carcinus maenas Hiat1–sham]) at (i) pH 7.5 as referred to in panel (A), (ii) medium containing 1 mmol L−1 NH4Cl, and (iii) medium without Na+. Positive bars represent higher and negative bars represent lower MA/MA+ uptake of Carcinus maenas Hiat1-expressing oocytes relative to sham-injected oocytes. Asterisk indicates significant differences of MA/MA+ uptake between sham-injected and Carcinus maenas Hiat1-expressing oocytes (without sham-subtraction). Daggers indicate significant differences of MA/MA+ uptake between control conditions (pH 7.5 sham-subtracted, light grey bar) and treatments (black bars, sham subtracted) (Student’s T-tests with P < 0.01, N = 20). Values are presented as means ± SE. Experiments have been conducted on two different batches of oocytes (i.e., different female, different days).
Figure 4. SIET measurements of net fluxes in Xenopus laevis oocytes expressing Carcinus maenas Hiat1. (A) NH4+ uptake (positive values, bath to oocyte) and (B) H+ release (negative values, oocyte to bath) kinetics of sham-injected (dotted line, empty circles) and Carcinus maenas Hiat1-expressing (solid line, black squares) oocytes in baths with increasing NH4Cl concentration. Asterisks in (A, B) denote significant differences between sham-injected and Carcinus maenas Hiat1-expressing oocytes with regards to either NH4+ or H+ flux at the given bath [NH4Cl] (two-way ANOVA with Bonferroni multiple comparisons, P < 0.05, N = 5). Values are presented as means ± SE. Experiments have been conducted on two different batch of oocytes (i.e., different female, different days).
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