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High resolution 3D perspective of Plasmodium biology: advancing into a new era

2011; Elsevier BV; Volume: 27; Issue: 12 Linguagem: Inglês

10.1016/j.pt.2011.08.002

1471-5007

Shiri Eshar, Noa Dahan-Pasternak, Allon Weiner, Ron Dzikowski,

Vector-borne infectious diseases

Apicomplexan parasites exhibit a great variety of complex life cycles that require adaptation to different niches of parasitism. They invade different host cells and highjack their biological functions. Plasmodium falciparum, responsible for the deadliest form of human malaria, causes disease while completely remodeling the erythrocytes of its human host through mechanisms that are only partly understood. Recent developments in ultrastructural technologies offer new opportunities to investigate fundamental aspects in the biology of the parasite in a three-dimensional (3D) perspective. Here we bring together recent work on host cell invasion, hemoglobin uptake, protein export and nuclear dynamics. A comprehensive 3D view of the ultrastructural biology of the parasite may shed new light on cellular mechanisms that underlie the pathogenicity of P. falciparum. Apicomplexan parasites exhibit a great variety of complex life cycles that require adaptation to different niches of parasitism. They invade different host cells and highjack their biological functions. Plasmodium falciparum, responsible for the deadliest form of human malaria, causes disease while completely remodeling the erythrocytes of its human host through mechanisms that are only partly understood. Recent developments in ultrastructural technologies offer new opportunities to investigate fundamental aspects in the biology of the parasite in a three-dimensional (3D) perspective. Here we bring together recent work on host cell invasion, hemoglobin uptake, protein export and nuclear dynamics. A comprehensive 3D view of the ultrastructural biology of the parasite may shed new light on cellular mechanisms that underlie the pathogenicity of P. falciparum. actin dependent tubular elongation that arise from the cytostome into the parasite cytoplasm. These tubes were suggested to either bud-off to small hemoglobin vacuoles or be directly connected to the food vacuole. 'cell mouth,' a feature used in some protozoan parasite for nutrient ingestion. In P. falciparum the cytostome is involved in hemoglobin uptake from the cytoplasm of the iRBCs. The cytostome is formed by endocytic invagination of the parasitophorous vacuole membrane and parasite plasma membrane into the cytoplasm of the parasite. loosely packed chromatin that allows access of the transcriptional machinery to the DNA and therefore is usually associated with transcriptionally active genes. In EM, euchromatin is usually seen as electron loose genetic material. exported trafficking system of a membrane network that is established by P. falciparum in the red blood cell cytoplasm. Two of the main features of the exomembrane system are the tubulovesicular network and Maurer's clefts. tightly packed chromatin that does not allow transcription to happen and therefore associated with inactive genes. In EM, heterochromatin is usually seen as electron dense genetic material. an actin dependent endocytotic process that mediates nutrient uptake. one of two main features of the exomembrane system. A single membrane flattened cisternae found adjacent to the membrane of iRBCs. Maurer's clefts are characterized by a translucent lumen and an electron-dense coat of variable thickness. Maurer's clefts are an intermediate compartment for protein export from the parasite to the host cell membrane. a complex of ∼30 proteins that form a pore at the nuclear envelope and mediate transport of molecules between the nucleoplasm and the cytoplasm of eukaryotic cells. actin independent large vesicle, which is claimed to be involved in hemoglobin uptake of late stage parasites by engulfing iRBC cytoplasm. double membrane vesicles that originate from the cytostome and carry hemoglobin into the food vacuole. described as an actin independent mechanism by which ring stage parasites fold on themselves and take the first gulp of host cell cytoplasm. one of two main features of the exomembrane system. It is formed by extensions of the parasitophorous vacuole membrane into the host cell cytoplasm. The TVN has a role in protein trafficking from the parasite to the host cell. because of the limited tilt range possible in electron tomography, information from high tilt angles, normally above 70°, is not possible. This causes an artifact in the tomographic reconstruction, known as the 'missing wedge.' Thus, the 3D volume obtained will contain some elongation and smearing in the axial plane. a process in which multiple sequential thin sections are collected and imaged by TEM. The images can later be aligned to form a 3D model. sequential thick sections are used for imaging by tomography following immuno-gold labeling of a specific protein before fixation. Tomograms are later merged to obtain a large volume 3D model. image acquisition technique in which a focused ion beam is used to mill slices as thin as 10 nm from a sample embedded in plastic. Between two millings a scanning electron beam is used to acquire an image of the newly revealed surface. Thus, by repeating this 'slice and view' procedure, an entire 3D volume can be acquired. light microscopy techniques that use various approaches to break the diffraction limit of light and obtain images in enhanced resolution. a super resolution technique in which illumination with multiple interfering beams of light permits optical tomography of fluorescently labeled samples at a resolution of ∼100 nm in the vertical plane and ∼300 nm in the axial plane. image acquisition technique involving gathering projection data from multiple directions and reconstructing it to obtain a 3D volume. a computational process in which a series of projected images acquired from multiple directions is used to compute a 3D volume data set.