Membrane knobs of unfixed Babesia bovis-infected erythrocytes: new findings as revealed by atomic force microscopy and surface potential spectroscopy

Aikawa, Masamichi; Kawazu, Shin-ichiro; Kamio, Tujihiko; Matsumoto, Yoshitsugu; Naya, Toshimitsu; Torii, Motomi; Ito, Yoshihiro; Tandler, Bernard; Nakano, Yamaji; Takeuchi, Tsutomu; Shiraishi, Soshi; Kanamura, Kiyoshi

doi:10.1016/s1383-5769(97)00031-7

Cited by 19 publications

(25 citation statements)

References 10 publications

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“…Previous atomic force microscopy on P falciparum-infected erythrocytes has demonstrated the knob structure has a positive charge, whereas the rest of the erythrocyte surface is negatively charged. 43 The protrusion of the knob with the cytoadherence molecule PfEMP1 may be necessary to elevate this positive charge for adherence to negatively charged endothelial plasma membranes. 44 Other mechanisms of interaction, which are not related to differences in charge, might also be involved.…”

Section: Discussionmentioning

confidence: 99%

“…The knobs formed from full-length KAHRP showed an average diameter of 120 nm and height of 17.5 nm, in accordance with earlier studies on P falciparum-infected erythrocytes. 45 It has been reported that knobs are not single entities but composed of a small and a larger subunit, 43 although a second study suggested these pre-knobs were artifacts from a faulty or double probe tip. 46 We have looked at the knob structure formed from full-length KAHRP in detail and found small elevations (preknobs) are often associated with the knob proper suggesting they are not artifacts.…”

Section: Org Frommentioning

confidence: 99%

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The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes

Rug

Prescott

Fernandez

et al. 2006

Blood

143

153

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Surface protrusions of Plasmodium falciparum-infected erythrocytes, called knobs, display focal aggregates of P falciparum erythrocyte membrane protein 1 (PfEMP1), the adhesion ligand binding endothelial-cell receptors. The resulting sequestration of infected erythrocytes in tissues represents an important factor in the course of fatalities in patients with malaria. The main component of knobs is the knob-associated histidine-rich protein (KAHRP), and it contributes to altered mechanical properties of parasiteinfected erythrocytes. The role of KAHRP domains in these processes is still elusive. We generated stable transgenic P falciparum-infected erythrocytes expressing mutant versions of KAHRP. Using atomic force and electron microscopy we show that the C-terminal repeat region is critical for the formation of functional knobs. Elasticity of the membrane differs dramatically between cells with different KAHRP mutations. We propose that the 5 repeat region of KAHRP is important in cross-linking to the host-cell cytoskeleton and this is required for knob protrusion and efficient adhesion under physi- IntroductionPlasmodium falciparum is the most lethal malaria parasite of humans. 1 An important aspect in virulence of P falciparum is the ability of infected erythrocytes to sequester in and obstruct the microvasculature of different organs. 2 These abnormal circulatory properties of erythrocytes involve parasite-induced alterations in their biomechanical and adhesive properties and are important for survival and pathogenicity of P falciparum. 3 Cytoadhesion is mediated by the antigenically variant P falciparum erythrocyte membrane protein-1 (PfEMP1), which can bind to host receptors including CD36 and chondroitin sulfate A (CSA). 4 PfEMP1 is concentrated on electron-dense elevations of the membrane referred to as knobs, 5-7 providing a platform for adherence under physiologic flow conditions. 8 Increased erythrocyte rigidity and adhesiveness result in dramatically augmented hemodynamic resistance observed in microvasculature perfused with P falciparum-infected erythrocytes. 9 Knobs consist predominantly of the knob-associated histidine-rich protein (KAHRP), 10,11 assembling on the cytoplasmic face of the membrane. KAHRP is required for knob formation. 8 KAHRP has a signal sequence with a recessed hydrophobic core that directs the protein into the parasitophorous vacuole via the endomembrane system. 12 A second signal, we termed the "Plasmodium export element" (PEXEL), 13 is required for transfer across the parasitophorous vacuole membrane to the erythrocyte cytosol. 13,14 The PEXEL is followed by a histidine-rich region containing sequences responsible for interaction with Maurer clefts, 15 structures assembled in the P falciparum-infected erythrocyte cytosol important in protein sorting and trafficking. 12 There are also 2 blocks of highly charged repeats, designated the 5Ј and 3Ј repeats according to their location. 10,11 Current evidence suggests KAHRP interacts with various cytoskeletal components of the erythr...

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Section: Discussionmentioning

confidence: 99%

Section: Org Frommentioning

confidence: 99%

The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes

Rug

Prescott

Fernandez

et al. 2006

Blood

143

153

View full text Add to dashboard Cite

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“…We used a BioScope AFM (Digital Instruments, USA) and a Nanoscope IIIa control station (Digital Instruments) with an Extender Electronics Module (Digital Instruments), as described previously (Aikawa et al 1996). Information on sample height was obtained by AFM and information about charge by surface potential microscopy (SPS).…”

Section: Merozoite Preparation For Atomic Force Microscopymentioning

confidence: 99%

Effects of dipyridamole on Plasmodium falciparum -infected erythrocytes

Akaki

Nakano

Ito

et al. 2002

Parasitology Research

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Electric charges on the surface of Plasmodium falciparum merozoites and erythrocytes were investigated by atomic force microscopy with surface potential spectroscopy. The apical end of merozoites was positively charged, while the entire erythrocyte surface was negatively charged. Transmission electron microscopy also demonstrated that negatively charged nanogold particles attached to the apical end of merozoites, and cationized ferritin particles attached to the entire surface of the erythrocyte. This indicates that the surface charge at the apical end of the merozoite may play an important role in invasion of the erythrocyte.

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“…In addition, surface charges can also be measured by surface potential spectroscopy (SPS), a component of the AFM system (Yokoyama and Inoue 1994). Recently, this system revealed that knobs on erythrocytes infected by Plasmodium falciparum and Babesia bovis have a positive charge (Aikawa et al 1996(Aikawa et al , 1997.…”

Section: Introductionmentioning

confidence: 99%

Invasive forms of Toxoplasma gondii, Leishmania amazonensis and Trypanosoma cruzi have a positive charge at their contact site with host cells

et al. 2001

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We examined the surface charges of invasive forms of Toxoplasma gondii, Leishmania amazonensis, and Trypanosoma cruzi by atomic force microscopy and surface potential spectroscopy. We found that the specific part of the protozoan which makes initial contact with the host cell is positively charged. This indicates that the positive charge at the site of contact facilitates binding of the invasive protozoan to negatively charged host cells.

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Membrane knobs of unfixed Babesia bovis-infected erythrocytes: new findings as revealed by atomic force microscopy and surface potential spectroscopy

Cited by 19 publications

References 10 publications

The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes

The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes

Effects of dipyridamole on Plasmodium falciparum -infected erythrocytes

Invasive forms of Toxoplasma gondii, Leishmania amazonensis and Trypanosoma cruzi have a positive charge at their contact site with host cells

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