Molecular, immunological, and physiological evidences of a sphingosine-activated plasma membrane Ca2+-channel in Trypanosoma equiperdum

Unmasking the Mechanism behind Miltefosine: Revealing the Disruption of Intracellular Ca2+ Homeostasis as a Rational Therapeutic Target in Leishmaniasis and Chagas Disease

“…Interestingly, the parasite channel is also a miltefosine target [10,11] and resembles the effect of the natural sphingolipid, not only in its interaction with the Ca 2+ channel but also in its molecular structure, as can be seen in Figure 1. This is also the case of the Ca 2+ channel recently reported for T. equiperdum [33], a trypanosomatid that infects horses, which is somehow different to the other channels found in human parasites described above. This will be discussed in the next section, which is focused on the mechanism of action of this drug on trypanosomatids.…”

“…In fact, CaM is able to directly interact with three different domains of human Ca 2+ channel, conferring, among other properties, Ca 2+ inactivation [54]. Taking into consideration that the trypanosomatid Ca 2+ channel possesses IQ domains [33] that are characteristic of CaM-binding domains, and that trypanopsomatids possess large quantities of CaM with an unique amino acidic sequence with 17 substitutions, it would be interesting to study the effect of CaM in relation to the effect of miltefosine and sphingosine on this Ca 2+ channel.…”