H+ channels in embryonic Biomphalaria glabrata cell membranes: Putative roles in snail host-schistosome interactions

Abstract

The human blood fluke Schistosoma mansoni causes intestinal schistosomiasis, a widespread neglected tropical disease. Infection of freshwater snails Biomphalaria spp. is an essential step in the transmission of S. mansoni to humans, although the physiological interactions between the parasite and its obligate snail host that determine success or failure are still poorly understood. In the present study, the B. glabrata embryonic (Bge) cell line, a widely used in vitro model for hemocyte-like activity, was used to investigate membrane properties, and assess the impact of larval transformation proteins (LTP) on identified ion channels. Whole-cell patch clamp recordings from Bge cells demonstrated that a Zn2+-sensitive H+ channel serves as the dominant plasma membrane conductance. Moreover, treatment of Bge cells with Zn2+ significantly inhibited an otherwise robust production of reactive oxygen species (ROS), thus implicating H+ channels in the regulation of this immune function. A heat-sensitive component of LTP appears to target H+ channels, enhancing Bge cell H+ current over 2-fold. Both Bge cells and B. glabrata hemocytes express mRNA encoding a hydrogen voltage-gated channel 1 (HVCN1)-like protein, although its function in hemocytes remains to be determined. This study is the first to identify and characterize an H+ channel in non-neuronal cells of freshwater molluscs. Importantly, the involvement of these channels in ROS production and their modulation by LTP suggest that these channels may function in immune defense responses against larval S. mansoni.

Voltage and pH sensing by the voltage-gated proton channel, HV1

“…V m is membrane potential. cell ↑pH i ↓pH o regulate V m charge compensation dinoflagellates trigger bioluminescent flash [ 1 , 3 ]; feeding [ 2 ] proton action potential [ 3 ] coccolithophores calcification [ 10 ] insect acid extrusion [ 11 ] snail neurons acid extrusion [ 4 , 12 , 13 ] acidification of confined spaces [ 14 ] ROS production for host defence [ 15 ] amphibian oocyte maturation, fertilization [ 16 , 17 ] V m oscillations [ 18 ] zebra fish neutrophils [ 19 ] respiratory epithelium acid extrusion [ 20 ] optimize pH of airway surface fluid [ 21 ]; CO 2 extrusion [ 22 ] facilitate DUOX1 activity [ ...…”

Unveiling the gene repertoire evolutionary dynamics driving repeated transitions out of the sea across molluscs

“…the prototypical or most representative observation of each cluster; see Methods), is composed of orthogroups broadly related to immunity and defense (Table S13). HVCN1 is a voltage-gated proton channel that has been shown to be involved in production of reactive oxygen species (ROS) linked to defense against parasitic infections in the freshwater snail Biomphalaria glabrata (Wright et al 2017). Another member of this cluster, MGST1, is a microsomal GST (see above), enzymes with broad antioxidant and defense functions, while QPCT (a glutaminyl-peptide cyclotransferase) has been involved in posttranslational modification of snail toxins (Buczek et al 2005;Gorson et al 2015).…”

Genomic Insights into Mollusc terrestrialization: Parallel and Convergent Gene Family Expansions as Key Facilitators in out-of-the-sea transitions

“…HVCN1 is a voltage-gated proton channel that has been shown to be involved in production of reactive oxygen species (ROS) linked to defense against parasitic infections in the freshwater snail Biomphalaria glabrata (Wright et al 2017). Another member of this cluster, MGST1, is a microsomal GST (see above), enzymes with broad antioxidant and defense functions, while QPCT (a glutaminyl-peptide cyclotransferase) has been involved in post-translational modification of snail toxins (Buczek et al 2005;Gorson et al 2015).…”