Pinning down prion pathogenesis In Nature, studies of how prions travel and suggestions for improved
diagnostics By Jeffrey M Perkel
Just how PrPC converts from a conformational variant of a normal cellular protein to PrPSc, the disease-
causing prion protein in transmissible spongiform encephalopathies (TSEs) like scrapie and Creutzfeldt-
Jakob disease, is poorly understood. Two new reports in Nature could help clarify the picture. Taken
together, these papers suggest potential points for therapeutic intervention and diagnostics
development, provided that critical molecular components can be isolated and the results verified.
In one report, Adriano Aguzzi, professor at the Institute of Neuropathology, University Hospital of
Zurich, and colleagues investigated the mechanisms by which prions get from the primary site of infection-
the immune system-to the nervous system. Aguzzi's group focused on the spleen, he said, because
there are nerves there and because the spleen's follicular dendritic cells (FDCs) are the main
immune reservoir for prions. The team therefore asked what would happen if they artificially
brought the FDCs closer to splenic nerves by using a CXCR5 knockout mouse (Nature, 425:717-720,
October 16, 2003).
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Spontaneous cellular fusion Cell fusion studies show bone-marrow-derived cells fuse with brain,
heart, and liver cells By David Secko
Bone marrow cells have the ability to differentiate into other cell types, for example, forming new
neurons, cardiomyocytes, or hepatocytes. It has been suggested that this is achieved by either the
conversion of one cell into another (transdifferentiation) or the combination of two cell types
together (cell fusion), but direct evidence in support of either thesis has been lacking. In the
October 12 advanced online Nature, Manuel Alvarez-Dolado and colleagues at the University of
California at San Francisco report a Cre/lox recombination method that detects cell fusion events
and demonstrates that bone-marrow-derived cells (BMDCs) fuse with other cells in vivo (Nature,
DOI:10.1038/nature02069, October 12, 2003).
Cells 'help' malaria invade Plasmodium hijacks cellular responses to hepatocyte growth factor,
facilitating invasion By Xavier Bosch
Human malarial infection begins following hepatocyte invasion by Plasmodium sporozoites injected
into the bloodstream during feeding by the mosquito vector. Before invasion, sporozoites traverse
the cytoplasm a number of hepatocytes, breaching plasma membranes and releasing growth factors and
proteins into the extracellular milieu. In the October 12 Nature Medicine, Margarida Carrolo and
colleagues at the Instituto Gulbenkian de Ciência report that wounding of hepatocytes by sporozoite
migration induces the secretion of hepatocyte growth factor (HGF). This then interacts with its
receptor MET, triggering a pathway leading to the rearrangement of the internal cytoskeleton of
neighboring cells, rendering them susceptible to infection (Nature Medicine, DOI:10.1038/nm947,
October 12, 2003).
Think big, think yeast Genome-wide protein tagging provides a global picture of protein levels and
localization By David Secko
Yeast was the first eukaryote to have its genome sequenced. Technologies that allow the global
analysis of cellular function have been pioneered with it, and genome-wide analysis of mRNA and
protein abundance, gene function, and protein-protein interactions have been undertaken on it.
However, we are still far from a comprehensive knowledge of how yeast functions. Two papers from the
Howard Hughes Medical Institute, University of California, San Francisco, in the October 16 Nature
report global studies of the yeast proteome that attempt to reveal the location and level of every
yeast protein.
Both groups tagged all the annotated open-reading frames (ORFs) in the yeast genome with either
green fluorescent protein (GFP) or a tandem affinity purification tag (TAP), followed by their
homologous recombination into the yeast genome to each gene';s original chromosomal location,
thereby creating a collection of protein-tagged strains
Kind Regards, Robert Karl Stonjek.