Campus Units
Biomedical Sciences
Document Type
Article
Publication Version
Accepted Manuscript
Publication Date
7-2015
Journal or Book Title
Molecular and Biochemical Parasitology
Volume
202
Issue
1
First Page
29
Last Page
37
DOI
10.1016/j.molbiopara.2015.09.001
Abstract
The neuromuscular system of helminths controls a variety of essential biological processes and therefore represents a good source of novel drug targets. The neuroactive substance, acetylcholine controls movement of Schistosoma mansoni but the mode of action is poorly understood. Here, we present first evidence of a functional G protein-coupled acetylcholine receptor in S. mansoni, which we have named SmGAR. A bioinformatics analysis indicated that SmGAR belongs to a clade of invertebrate GAR-like receptors and is related to vertebrate muscarinic acetylcholine receptors. Functional expression studies in yeast showed that SmGAR is constitutively active but can be further activated by acetylcholine and, to a lesser extent, the cholinergic agonist, carbachol. Anti-cholinergic drugs, atropine and promethazine, were found to have inverse agonist activity towards SmGAR, causing a significant decrease in the receptor’s basal activity. An RNAi phenotypic assay revealed that suppression of SmGAR activity in early-stage larval schistosomulae leads to a drastic reduction in larval motility. In sum, our results provide the first molecular evidence that cholinergic GAR -like receptors are present in schistosomes and are required for proper motor control in the larvae. The results further identify SmGAR as a possible candidate for antiparasitic drug targeting.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
Copyright Owner
Elsevier B.V.
Copyright Date
2015
Language
en
File Format
application/pdf
Recommended Citation
MacDonald, Kevin; Kimber, Michael J.; Day, Timothy A.; and Ribeiro, Paula, "A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni" (2015). Biomedical Sciences Publications. 51.
https://lib.dr.iastate.edu/bms_pubs/51
Included in
Parasitic Diseases Commons, Veterinary Microbiology and Immunobiology Commons, Veterinary Preventive Medicine, Epidemiology, and Public Health Commons, Veterinary Toxicology and Pharmacology Commons
Comments
This is a manuscript of an article published as MacDonald, Kevin, Michael J. Kimber, Tim A. Day, and Paula Ribeiro. "A constitutively active G protein-coupled acetylcholine receptor regulates motility of larval Schistosoma mansoni." Molecular and biochemical parasitology 202, no. 1 (2015): 29-37. doi: 10.1016/j.molbiopara.2015.09.001. Posted with permission.