Doublet microtubules (DMTs) are flagellar components required for the protist ( ) to swim through the human genitourinary tract to cause trichomoniasis, the most common non-viral sexually transmitted disease. Lack of DMT structures has prevented structure-guided drug design to manage infection. Here, we determined the cryo-EM structure of native DMTs, identifying 29 unique proteins, including 18 microtubule inner proteins and 9 microtubule outer proteins.
View Article and Find Full Text PDF, a common sexually transmitted parasite that colonizes the human urogenital tract, secretes extracellular vesicles (TvEVs) that are taken up by human cells and are speculated to be taken up by parasites as well. While the crosstalk between TvEVs and human cells has led to insight into host:parasite interactions, roles for TvEVs in infection have largely been one-sided, with little known about the effect of TvEV uptake by . Approximately 11% of infections are found to be coinfections of multiple strains.
View Article and Find Full Text PDFTrichomonas vaginalis is a human infective parasite responsible for trichomoniasis-the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis resides exclusively in the urogenital tract of both men and women.
View Article and Find Full Text PDF, the causative pathogen for the most common nonviral sexually transmitted infection worldwide, is itself frequently infected with one or more of the four types of small double-stranded RNA (dsRNA) viruses (TVV1 to 4, genus , family ). Each TVV encloses a nonsegmented genome within a single-layered capsid and replicates entirely intracellularly, like many dsRNA viruses, and unlike those in the family. Here, we have determined the structure of TVV2 by cryo-electron microscopy (cryoEM) at 3.
View Article and Find Full Text PDFThe significance of lipid droplets in lipid metabolism, cell signaling, and regulating longevity is increasingly recognized, yet the lipid droplet's unique properties and architecture make it difficult to size and study using conventional methods. To begin to address this issue, we demonstrate the capabilities of nanoparticle tracking analysis (NTA) for sizing of lipid droplets. NTA was found to be adequate to assess lipid droplet stability over time, indicating that lipid droplet preparations are stable for up to 24 h.
View Article and Find Full Text PDFMacroautophagy is a cellular degradation process responsible for the clearance of excess intracellular cargo. Existing methods for bulk quantification of autophagy rely on organelle markers that bind to multiple autophagy organelle types, making it difficult to tease apart the subcellular mechanisms implicated in autophagy dysfunction in liver and other pathologies. To address this issue, methods based on individual organelle measurements are needed.
View Article and Find Full Text PDFVariant surface glycoprotein (VSG) is central to antigenic variation in African trypanosomes. Although much prior work documents that VSG is efficiently synthesized and exported to the cell surface, it was recently claimed that 2-3 fold more is synthesized than required, the excess being eliminated by ER-Associated Degradation (ERAD) (Field et al., ).
View Article and Find Full Text PDFEfficient separations of particles with micron and submicron dimensions are extremely useful in preparation and analysis of materials for nanotechnological and biological applications. Here, we demonstrate a nonintuitive, yet efficient, separation mechanism for μm and subμm colloidal particles and organelles, taking advantage of particle transport in a nonlinear post array in a microfluidic device under the periodic action of electrokinetic and dielectrophoretic forces. We reveal regimes in which deterministic particle migration opposite to the average applied force occurs for a larger particle, a typical signature of deterministic absolute negative mobility (dANM), whereas normal response is obtained for smaller particles.
View Article and Find Full Text PDFThe multivesicular body (MVB) is a specialized Rab7+ late endosome (LE) containing multiple intralumenal vesicles that function in targeting ubiquitinylated cell surface proteins to the lysosome for degradation. African trypanosomes lack a morphologically well-defined MVB, but contain orthologs of the ESCRT (Endosomal Sorting Complex Required for Transport) machinery that mediates MVB formation. We investigate the role of TbVps23, an early ESCRT component, and TbVps4, the terminal ESCRT ATPase, in lysosomal trafficking in bloodstream form trypanosomes.
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