Functional characterization of the Ca2+-ATPase SMA1 from Schistosoma mansoni

Abstract

is a parasite that causes bilharzia, a neglected tropical disease affecting hundreds of millions of people each year worldwide. In 2012, had been identified as the only invertebrate possessing two SERCA-type Ca-ATPases, SMA1 and SMA2. However, our analysis of recent genomic data shows that the presence of two SERCA pumps is rather frequent in parasitic flatworms. To understand the reasons of this redundancy in , we compared SMA1 and SMA2 at different levels. In terms of sequence and organization, the genes and are similar, suggesting that they might be the result of a duplication event. At the protein level, SMA1 and SMA2 only slightly differ in length and in the sequence of the nucleotide-binding domain. To get functional information on SMA1, we produced it in an active form in, as previously done for SMA2. Using phosphorylation assays from ATP, we demonstrated that like SMA2, SMA1 bound calcium in a cooperative mode with an apparent affinity in the micromolar range. We also showed that SMA1 and SMA2 had close sensitivities to cyclopiazonic acid but different sensitivities to thapsigargin, two specific inhibitors of SERCA pumps. On the basis of transcriptomic data available in GeneDB, we hypothesize that SMA1 is a housekeeping Ca-ATPase, whereas SMA2 might be required in particular striated-like muscles like those present the tail of the cercariae, the infecting form of the parasite.

Ca2+ Signaling and Regeneration

“…Contrasting with C. elegans, planarians express voltage-gated sodium channels, hyperpolarization-activated cyclic nucleotide-gated channels, and two-pore channels. Flatworms are also endowed with a diverse Ca 2+ signaling toolbox, containing homologs for intracellular Ca 2+ release channels and organellar Ca 2+ pumps, components supporting store-operated Ca 2+ entry (STIM, Orai), as well as cell-surface Ca 2+ transporters and numerous Ca 2+ -binding proteins (Prole and Taylor 2011;Zhang et al 2013;Marechal et al 2018). In terms of neurophysiology, intact worms are clearly receptive to a broad range of environmental stimuli, likely mediated through sensory neurons expressing a broad portfolio of planarian TRP channels (≥30 sequences) that reside within the epidermis and submuscular nervous plexus (Inoue et al 2014(Inoue et al , 2015Arenas et al 2017).…”