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. 2022 Feb;117(2):274-292.
doi: 10.1111/mmi.14811. Epub 2021 Sep 22.

KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in Plasmodium falciparum-infected erythrocytes

Cecilia P Sanchez  1 , Pintu Patra  2   3 , Shih-Ying Scott Chang  4 , Christos Karathanasis  5 , Lukas Hanebutte  1 , Nicole Kilian  1 , Marek Cyrklaff  1 , Mike Heilemann  3   5 , Ulrich S Schwarz  2   3 , Mikhail Kudryashev  4 , Michael Lanzer  1
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Free article

KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in Plasmodium falciparum-infected erythrocytes

Cecilia P Sanchez et al. Mol Microbiol. 2022 Feb.
Free article

Abstract

The knob-associated histidine-rich protein (KAHRP) plays a pivotal role in the pathophysiology of Plasmodium falciparum malaria by forming membrane protrusions in infected erythrocytes, which anchor parasite-encoded adhesins to the membrane skeleton. The resulting sequestration of parasitized erythrocytes in the microvasculature leads to severe disease. Despite KAHRP being an important virulence factor, its physical location within the membrane skeleton is still debated, as is its function in knob formation. Here, we show by super-resolution microscopy that KAHRP initially associates with various skeletal components, including ankyrin bridges, but eventually colocalizes with remnant actin junctions. We further present a 35 Å map of the spiral scaffold underlying knobs and show that a KAHRP-targeting nanoprobe binds close to the spiral scaffold. Single-molecule localization microscopy detected ~60 KAHRP molecules/knob. We propose a dynamic model of KAHRP organization and a function of KAHRP in attaching other factors to the spiral scaffold.

Keywords: actin; ankyrin; erythrocyte; malaria; microscopy; virulence factor.

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