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United States Department of Agriculture

Agricultural Research Service

Title: Functional Characterization of the Putative Orphan Neuropeptide G-Protein Coupled Receptor C26F1.6 in Caenorhabditis Elegans

Authors
item Mertens, Inge - CATHOLIC UNIV, BELGIUM
item Vandingenen, Anick - CATHOLIC UNIV, BELGIUM
item Meeussen, Tom - CATHOLIC UNIV, BELGIUM
item Janssen, Tom - CATHOLIC UNIV, BELGIUM
item Luyten, Walter - CATHOLIC UNIV, BELGIUM
item Nachman, Ronald
item DE Loof, Arnold - CATHOLIC UNIV, BELGIUM
item Schoofs, Liliane - CATHOLIC UNIV, BELGIUM

Submitted to: Federation of European Biochemical Societies Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: July 14, 2004
Publication Date: August 27, 2004
Citation: Mertens, I., Vandingenen, A., Meeussen, T., Janssen, T., Luyten, W., Nachman, R.J., De Loof, A., Schoofs, L. 2004. Functional characterization of the putative orphan neuropeptide G-protein coupled receptor C26F1.6 in Caenorhabditis elegans. Federation of European Biochemical Societies Letters. 573:55-60.

Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling invertebrate pests such as insects and nematode worms. The basic premise of this research is that 'FMRFamide' neuropeptides (short chains of amino acids) serve as potent messengers in invertebrates such as nematode worms and insects to regulate vital functions. Nevertheless, these neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest, and inability to pass through the outside skin and/or digestive tract. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest invertebrates and interact with the active site within an agricultural or medical pest in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. We report on the isolation, identification and characterization of a third active site for the 'FMRFamide' class of invertebrate neuropeptides from the nematode labeled 'C. elegans', a prime model for parasitic nematode worms that plague man, livestock and crops. Key structural features of the neuropeptides have been identified that allow them to turn this active site on. This discovery will aid in the design of neuropeptide-like compounds capable of disrupting critical life functions in nematode worms. This work represents a spin-off of our primary focus on insect pests and brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling invertebrate pests, including nematode worms and insects, in an environmentally friendly fashion.

Technical Abstract: In this study, we describe the cloning and the characterization of the third FaRP (FMRFamide related peptide) receptor in C. elegans, the VRFa receptor 1. Numerous structurally different FaRPs were synthesized and used to screen the orphan C26F1.6 receptor for activation. Two peptides ending in M(orL)VRFamide elicited a calcium response in receptor expressing mammalian cells. The response is dose-dependent and appeared to be very specific, since very closely related FaRPs were less active, even the other peptides ending in M(orL)VRFamide. Pharmacological profiling of the most active peptide suggests that SMVRFa is the most active binding core. N-terminal extension decreases peptide activity.

Last Modified: 4/17/2014
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