Weibel-Palade bodies (WPBs) comprise an on-demand storage organelle within vascular endothelial cells. It's major component, the hemostatic protein von Willebrand factor (VWF), is known to assemble into long helical tubules and is hypothesized to drive WPB biogenesis. However, electron micrographs of WPBs at the Golgi apparatus show that these forming WPBs contain very little tubular VWF compared with mature peripheral WPBs, which raises questions on the mechanisms that increase the VWF content and facilitate vesicle growth. Using correlative light and electron microscopy and electron tomography, we investigated WPB biogenesis in time. We reveal that forming WPBs maintain multiple connections to the Golgi apparatus throughout their biogenesis. Also by volume scanning electron microscopy, we confirmed the presence of these connections linking WPBs and the Golgi apparatus. From electron tomograms, we provided evidence that nontubular VWF is added to WPBs, which suggested that tubule formation occurs in the WPB lumen. During this process, the Golgi membrane and clathrin seem to provide a scaffold to align forming VWF tubules. Overall, our data show that multiple connections with the Golgi facilitate content delivery and indicate that the Golgi appears to provide a framework to determine the overall size and dimensions of newly forming WPBs.
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http://dx.doi.org/10.1182/blood-2014-10-608596 | DOI Listing |
Biol Pharm Bull
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Faculty of Pharmacy and Pharmaceutical Sciences, Josai University.
Ceramide (Cer) is synthesized in the endoplasmic reticulum (ER) using sphinganine as the common backbone and is then transported to the Golgi apparatus to synthesize two complex sphingolipids, sphingomyelin (SM) and glucosylceramide (GlcCer). Brefeldin A (BFA) affects the structure of the Golgi apparatus, resulting in the redistribution of the Golgi proteins into the ER. Therefore, BFA has been used to examine the ER-to-Golgi trafficking of lipids, but the detailed lipid changes in cells upon BFA treatment are not fully understood.
View Article and Find Full Text PDFVet Microbiol
December 2024
National Key Laboratory of Veterinary Public Health and Safety, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
Pseudorabies virus (PRV) poses a significant threat to the global swine breeding industry and public health, but how the virus transverses the host defense systems for efficient viral replication and pathogenesis remains unclear. Here, we report that PRV could inhibit the unfolded protein response (UPR), a critical component of host innate immunity against viral infection, to promote virus replication during the late infection stages. PERK was shown phosphorylated and active in PRV-infected cells, but the subsequent events were suppressed post virus infection, such as eIF2α phosphorylation, ATF4 expression, and the formation of stress granules (SGs).
View Article and Find Full Text PDFNat Commun
January 2025
Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
Despite the enormous significance of malaria parasites for global health, some basic features of their ultrastructure remain obscure. Here, we apply high-resolution volumetric electron microscopy to examine and compare the ultrastructure of the transmissible male and female sexual blood stages of Plasmodium falciparum as well as the more intensively studied asexual blood stages revisiting previously described phenomena in 3D. In doing so, we challenge the widely accepted notion of a single mitochondrion by demonstrating the presence of multiple mitochondria in gametocytes.
View Article and Find Full Text PDFFront Cell Dev Biol
December 2024
Departments of Biology, University of York, York, United Kingdom.
Nat Commun
December 2024
Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
Iron is a potent biochemical, and accurate homeostatic control is orchestrated by a network of interacting players at multiple levels. Although our understanding of organismal iron homeostasis has advanced, intracellular iron homeostasis is poorly understood, including coordination between organelles and iron export into the ER/Golgi. Here, we show that SLC39A13 (ZIP13), previously identified as a zinc transporter, promotes intracellular iron transport and reduces intracellular iron levels.
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