Latrophilin-like G protein-coupled receptor 1 (LAT-1) (LAT-1)

Nematode latrophilin-like G protein-coupled receptors, most notably LAT-1, are members of the adhesion G protein-coupled receptor (aGPCR) family and serve as critical targets for the cyclooctadepsipeptide class of anthelmintics, such as emodepside and its precursor PF1022A (Saeger et al., 2001; Willson et al., 2004). These receptors are primarily expressed in the nematode nervous system and pharyngeal muscle, where they regulate essential physiological processes including feeding (pharyngeal pumping), locomotion, and egg-laying (Guest et al., 2007). In parasitic nematodes, LAT-1 is a primary mediator of emodepside's inhibitory effects on the pharynx, contributing to the drug's broad-spectrum efficacy against various helminths (Welz et al., 2011). The binding of emodepside to LAT-1 is thought to activate a G protein-mediated signaling cascade that facilitates the opening of SLO-1 potassium channels, leading to neuromuscular hyperpolarization and flaccid paralysis (Crisford et al., 2011). Because these receptors are distinct from those in mammalian hosts, they represent a selective and effective target for treating both soil-transmitted and filarial nematode infections (Hübner et al., 2021).

Other names

LAT-1Latrophilin-1B0457.1HC110RAdhesion G protein-coupled receptor LAT-1Nematode latrophilin

Emodepside acts as an agonist at the latrophilin-like receptor (LAT-1), an adhesion G protein-coupled receptor. Activation of LAT-1 triggers a G protein-mediated signaling cascade (likely involving Gq/11 and phospholipase C) that facilitates the opening of SLO-1 large-conductance calcium-activated potassium channels, leading to hyperpolarization of neurons and muscles, resulting in flaccid paralysis and inhibition of feeding (pharyngeal pumping) in nematodes (Saeger et al., 2001; Guest et al., 2007; Welz et al., 2011).