Biochemical characterization of AeD7L2 and its physiological relevance in blood feeding in the dengue mosquito vector, Aedes aegypti

Abstract

When a mosquito inserts its mouth parts into the host skin, it causes tissue and vascular damage that triggers host hemostatic responses. Mosquito saliva is injected at the bite site to counteract the hemostasis and help blood‐feeding. D7 salivary proteins bind and scavenge several hemostasis agonists such as serotonin, norepinephrine, and U‐46619. Therefore, D7 proteins inhibit the action of the host molecules and prevent vasoconstriction and platelet aggregation.

Novel salivary antihemostatic activities of long-form D7 proteins from the malaria vector Anopheles gambiae facilitate hematophagy

“…aegypti AeD7L2, and Culex quinquefasciatus CxD7L2 ( Fig. S6 ) ( 3 , 14 , 16 , 22 , 26 , 27 , 28 ). Ae.…”

“…This function is similar to that of D7s from other mosquito species. AnSt-D7L1, AlboD7L1, CxD7L2, and AeD7L2 also bind U-46619 ( 16 , 22 , 27 , 28 ). Both AeD7L2 and AnSt-D7L1 were also shown to inhibit vascular contraction ( 16 , 27 ).…”

“…AnSt-D7L1, AlboD7L1, CxD7L2, and AeD7L2 also bind U-46619 ( 16 , 22 , 27 , 28 ). Both AeD7L2 and AnSt-D7L1 were also shown to inhibit vascular contraction ( 16 , 27 ). Serotonin is a complex substance that can be vasoactive and cause both vasoconstriction and vasodilation ( 35 ) and is a vasoconstrictive agonist of mesenteric arteries ( 36 ).…”

“…AlboD7L1 and CxD7L2 had a low U-46619–induced platelet inhibiting effect because of their low binding affinity to U-46619 ( 22 , 28 ). AnSt-D7L1 and AeD7L2, which both tightly bind U-46619, displayed a strong inhibition effect on platelet aggregation ( 16 , 27 ). Alone, serotonin is a weak agonist to platelet aggregation, but it can reduce the threshold concentration of other agonists, such as collagen.…”

Ramatroban-Based Analogues Containing Fluorine Group as Potential 18F-Labeled Positron Emission Tomography (PET) G-Protein Coupled Receptor 44 (GPR44) Tracers

“…Initially, ramatroban was found to bind to TP after displacing the TP antagonist [ 3 H]SQ29548 in a binding assay, resulting in an IC 50 of 68 nM [ 24 ]. Additional binding assays with TP agonist U-46619 [ 25 ] showed stronger antagonist binding to TP, with a lower IC 50 of 30 nM and K i of 10 nM [ 26 ]. The K d and B max of ramatroban were characterized as around 6 nM and 1177 binding sites/platelet, respectively [ 27 ].…”