Sensory Protein Kinase Signaling inSchistosoma mansoniCercariae: Host Location and Invasion

Abstract

Schistosoma mansoni cercariae display specific behavioral responses to abiotic/biotic stimuli enabling them to locate and infect the definitive human host. Here we report the effect of such stimulants on signaling pathways of cercariae in relation to host finding and invasion. Cercariae exposed to various light/temperature regimens displayed modulated protein kinase C (PKC), extracellular signal–regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) activities, with distinct responses at 37°C and intense light/dark, when compared to 24°C under normal light. Kinase activities were localized to regions including the oral sensory papillae, acetabular ducts, tegument, acetabular glands, and nervous system. Furthermore, linoleic acid modulated PKC and ERK activities concurrent with the temporal release of acetabular gland components. Attenuation of PKC, ERK, and p38 MAPK activities significantly reduced gland component release, particularly in response to linoleic acid, demonstrating the importance of these signaling pathways to host penetration mechanisms.

A next-generation microarray further reveals stage-enriched gene expression pattern in the blood fluke Schistosoma japonicum

“…F-box protein 25/32 (EZ000162), dual specificity mitogen-activated protein kinase 2 (AY815572), Serine/threonine kinase NLK (FN317434), Rho GTPase-activating protein 39 (FN317833), GDP/GTP exchange factor Sec2p domain containing protein (FN317362), Rho-associated protein kinase 1 (FN330915), mitogen-activated protein kinase 3 (EZ000180), Ran binding protein 9-related protein (AY812647), GTP-binding protein 2 (FN317377), NF-kappa-B inhibitor-interacting Ras-like protein 1 (AY812481), son of sevenless (AY915633), MAP kinase (AY594257), C-Jun-amino-terminal kinase-interacting protein 4 (AY808598), and regulator of G-protein signaling 7 (AY810841), were over-expressed in cercariae (Additional file 4: Table S3). These results support recent finding that three signaling pathways, extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and protein kinase C (PKC), are modulated in cercariae in response to light and temperature cues as well as the skin fatty acid linoleic acid (LA) and are important in host penetration mechanisms [65]. …”

Deep phosphoproteome analysis of Schistosoma mansoni leads development of a kinomic array that highlights sex-biased differences in adult worm protein phosphorylation

“…Motifs for proline-directed protein kinases were also well represented including PxSP for ERK/MAPK; this motif had 137 phosphorylation sites assigned. We have previously demonstrated a role for ERK in egg laying, pairing, and movement of adult S. mansoni [14], and invasion of the host by cercariae [72]. For the tyrosine phosphorylated peptides, only one motif was discovered (YxxL) (but within 280 peptides) which HPRD revealed is a target of JAK-2 kinase.…”

“…We have previously employed such antibodies to functionally study protein kinase (e.g. PKC [14,47], MAPK [14,57,72], Akt [15], PKA [13,50]) signalling in S. mansoni and the phosphorylation site data presented here offers further opportunity to either validate additional existing anti-phospho antibodies/develop new antibodies to facilitate the study of protein kinase signalling in schistosomes in various contexts (developmental, host-parasite interplay etc). Protein kinases also represent excellent drug targets and a growing number of protein kinase inhibitors have been approved for use in humans [77]; thus, protein kinases of schistosomes are being considered as possible therapeutic targets including through drug repurposing [5,20,21].…”

Molecular characterization of host-parasite cell signalling in Schistosoma mansoni during early development

“…Anti-actin antibodies (Sigma; 1:3000) were used to assess protein-loading differences. This was important because of difficulties experienced in obtaining equal numbers of parasites in each sample; phosphorylation levels were then normalised against differences in actin signal between samples 15 65 68 .…”