Kringle-containing transmembrane protein 1 (KREMEN1) (KREMEN1)

Kringle-containing transmembrane protein 1 (KREMEN1) is a host cell surface receptor that has been identified as the critical binding partner for the Plasmodium Apical Membrane Antigen 1 (AMA1) during the invasion of red blood cells (Gruszczyk et al., 2023). In Plasmodium vivax infection, PvAMA1 specifically interacts with KREMEN1 on the surface of immature reticulocytes to facilitate the formation of the moving junction, a vital step for parasite internalization (Arevalo-Pinzon et al., 2017). For many years, this receptor was described in scientific literature as an uncharacterized, neuraminidase- and chymotrypsin-sensitive protein, but recent structural and biochemical studies have confirmed its identity as KREMEN1. Beyond its role in malaria, KREMEN1 is a functional component of the Wnt signaling pathway, where it acts as a co-receptor for Dickkopf-1 (DKK1) to antagonize LRP6-mediated signaling (Mao et al., 2002). Targeting the PvAMA1-KREMEN1 interaction is a major focus of blood-stage malaria vaccine development, as blocking this attachment prevents the parasite from entering host cells and continuing its life cycle. Experimental vaccines and monoclonal antibodies are currently being investigated to disrupt this interaction and provide immunity against vivax malaria.

Other names

KRM1Kringle-containing protein marking the eye and the noseUncharacterized reticulocyte surface receptor bound by PvAMA-1Neuraminidase- and chymotrypsin-sensitive reticulocyte receptorUnknown erythrocytic receptor for PvAMA-1

Inhibition of merozoite invasion by blocking the interaction between the parasite ligand PvAMA-1 and the host receptor KREMEN1.