Abstract
Ticks, notorious blood-feeders and disease-vectors, have lost a part of their genetic complement encoding haem biosynthetic enzymes and are, therefore, dependent on the acquisition and distribution of host haem. Solute carrier protein SLC48A1, aka haem-responsive gene 1 protein (HRG1), has been implicated in haem transport, regulating the availability of intracellular haem. HRG1 transporter has been identified in both free-living and parasitic organisms ranging from unicellular kinetoplastids, nematodes, up to vertebrates. However, an HRG1 homologue in the arthropod lineage has not yet been identified. We have identified a single HRG1 homologue in the midgut transcriptome of the tick Ixodes ricinus, denoted as IrHRG, and have elucidated its role as a haem transporter. Data from haem biosynthesis-deficient yeast growth assays, systemic RNA interference and the evaluation of gallium protoporphyrin IX-mediated toxicity through tick membrane feeding clearly show that IrHRG is the bona fide tetrapyrrole transporter. We argue that during evolution, ticks profited from retaining a functional hrg1 gene in the genome because its protein product facilitates host haem escort from intracellularly digested haemoglobin, rendering haem bioavailable for a haem-dependent network of enzymes.
Highlights
Several parasites have, through evolution, lost genes encoding haem biosynthetic enzymes, yet they retained and perform haem-based metabolism [1]
The arthropod branch was further divided into acarids and insects, where our protein sequence clustered with haem-responsive gene (HRG) data obtained from other acarids
To verify whether IrHRG plays a role as a porphyrin transporter in vivo, we examined whether RNAi-mediated silencing of IrHRG in ticks (IrHRG-KD) can rescue gallium protoporphyrin IX (GaPPIX)-mediated toxicity in serum-fed ticks
Summary
Through evolution, lost genes encoding haem biosynthetic enzymes, yet they retained and perform haem-based metabolism [1]. The parasites need to salvage host haem and distribute it across their cells and body tissues in order to recycle the acquired host haem for their own metabolic demands. Cannot synthesize haem de novo and need to operate a regulated acquisition–distribution–disposal network to allow haem-based metabolism and, at the same time, prevent cytotoxicity resulting from haem overload [2]. The absence of dietary haem leads to the failure of engorged tick females to reproduce [3]. Such maternal haem is acquired as a liberated by-product of lysosomal digestion of host haemoglobin in tick midgut cells [3,4]. The manner in which haem is translocated into the cytosol of tick midgut digest cells is, unknown
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