期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 22, 页码 10290-10295出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1003666107
关键词
CAPA; Chagas'; G protein-coupled receptor; neurohormone; neuropeptide
资金
- Natural Sciences and Engineering Research Council (NSERC) Discovery
- US Department of Agriculture-National Research Initiative-Cooperative State Research, Education, and Extension Service [2007-35604-17759]
- Bionational Agricultural Research and Development [420509C]
- Deployed War-Fighter Protection Program Initiative [0500-32000001-01R]
- NSERC Canada
Diuresis following blood-gorging in Rhodnius prolixus is the major process leading to the transmission of Chagas' disease. We have cloned the cDNA of the first receptor known to be involved in an antidiuretic strategy in insects, a strategy that prevents diuresis. This receptor belongs to the insect CAPA receptor family known in other insects to be activated by peptides encoded within the capability gene. We characterize the expression profile in fifth-instars and find expression is localized to the alimentary canal. Highest transcript levels are found in Malpighian tubules and the anterior midgut, which are known targets of the antidiuretic hormone, RhoprCAPA-alpha 2. Two transcripts were identified, capa-r1 and capa-r2; however, the latter encodes an atypical G protein-coupled receptor lacking a region ranging between the first and second transmembrane domain. Our heterologous expression assay revealed the expressed capa-r1 receptor is activated by Rhopr-CAPA-alpha 2 (EC50 = 385nM) but not by RhoprCAPA-alpha 1. Structural analogs of the inactive RhoprCAPA-alpha 1 were capable of activating the expressed capa-r1 receptor, confirming the importance of the C-terminal consensus sequence common to CAPA-related peptides. In addition, this receptor has some sensitivity to the pyrokinin-related peptide, RhoprCAPA-alpha PK1, but with an efficacy approximate to 40-fold less than RhoprCAPA-alpha 2. Other peptides belonging to the PRX-amide superfamily were inactive on the capa-r1 receptor. Taken together, the neuroendocrinological relevance of this receptor in facilitating the antidiuretic strategy in R. prolixus may make this receptor a useful target for development of agonists or antagonists that could help influence the transmission of Chagas' disease that occurs during diuresis in this medically important insect-disease vector.
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