KAHRP dynamically relocalizes to remodeled actin junctions and associates with knob spirals in Plasmodium falciparum‐infected erythrocytes. Issue 2 (22nd September 2021)

• Record Type: Journal Article
• Authors: Sanchez, Cecilia P.; Patra, Pintu; Chang, Shih‐Ying Scott; Karathanasis, Christos; Hanebutte, Lukas; Kilian, Nicole; Cyrklaff, Marek; Heilemann, Mike; Schwarz, Ulrich S.; Kudryashev, Mikhail; Lanzer, Michael
• Is Part Of: Molecular microbiology. Volume 117:Issue 2(2022)
• Page Start: 274
• Page End: 292
• Publication Date: 2021-09-22
• Subjects: actin -- ankyrin -- erythrocyte -- malaria -- microscopy -- virulence factor; Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.14811
• Languages: English
• ISSNs: 0950-382X

Abstract

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. Abstract : In order to avoid clearance by the spleen, malaria‐infected erythrocytes adhere to the vascular endothelium by adhesive structures called knobs. We have used super‐resolution optical microscopy and electron tomography to demonstrate that their spiral structure results from the dynamical relocalization of the parasite‐secreted protein KAHRP.