Biomedical subjects

Ricardo Renzo Brentani

Publications and source records attributed to Ricardo Renzo Brentani.

3 recordsLinked to original sources

PubMed2004

PrPc on the road: trafficking of the cellular prion protein.

The glycosylphosphatidylinositol (GPI)-anchored cellular prion protein (PrPc) has a fundamental role in prion diseases. Intracellular trafficking of PrPc is important in the generation of protease resistant PrP species but little is known of how endocytosis affects PrPc function. Here, we discuss recent experiments that have illuminated how PrPc is internalized and what are the possible destinations taken by the protein. Contrary to what would be expected for a GPI-anchored protein there is increasing evidence that clathrin-mediated endocytosis and classical endocytic organelles participate in PrPc trafficking. Moreover, the N-terminal domain of PrPc may be involved in sorting events that can direct the protein during its intracellular journey. Indeed, the concept that the GPI-anchor determines PrPc trafficking has been challenged. Cellular signaling can be triggered or be regulated by PrPc and we suggest that endocytosis of PrPc may influence signaling in several ways. Definition of the processes that participate in PrPc endocytosis and intracellular trafficking can have a major impact on our understanding of the mechanisms involved in PrPc function and conversion to protease resistant conformations.

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PubMed2002

Galectin-3 modulates carbohydrate-dependent thymocyte interactions with the thymic microenvironment.

The process of thymocyte differentiation occurs within the context of the thymic microenvironment, in which T cell precursors interact with thymic microenvironmental cells and extracellular matrix. Here we studied the expression of galectin-3, a beta-galactoside binding lectin, in the thymus of young adult mice. Galectin-3 was found mainly in the medulla and to a lesser extent in the cortex. We further showed that distinct microenvironmental elements, such as thymic epithelial cells, the epithelial component of thymic nurse complexes and phagocytic cells of the thymic reticulum produce, secrete and accumulate galectin-3 on the cell surface. Functionally, galectin-3-enriched medium inhibited in vitro thymocyte interactions with thymic microenvironmental cells, accelerated the release of thymocytes from thymic nurse cells and inhibited the reconstitution of these lymphoepithelial complexes. These effects were blocked by exogenous lactose (Galbeta1-4Glc), but not melibiose (Galalpha1-6Glc), and by a monospecific anti-galectin-3 antibody. Recombinant galectin-3 also inhibited thymocyte/thymic epithelial cell interactions. Our data indicate that intrathymically produced galectin-3 disrupts thymocyte/microenvironmental cell interactions, thus acting as a de-adhesion molecule.

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PubMed2002

The biology of the cellular prion protein.

Prions are the etiological agents for infectious degenerative encephalopaties acting by inducing conformational changes in the cellular prion protein (PrPc), which is a cell membrane GPI anchored glycoprotein. Besides its conservation among species and expression in most tissues, and in particular, in high levels in the nervous system, the role for cellular prion protein remained obscure for some time. Initial skepticism about such a role was mainly due to the absence of a gross phenotype alteration in cellular prion protein null mice. In the last few years, some possible biological functions for cellular prion protein have been described. Copper binds to the molecule and the resulting complex may be responsible for cell protection against oxidative stress. Cellular prion protein is also a high-affinity ligand for laminin, and induces neuronal cell adhesion, neurite extension and maintenance. The binding site resides in a carboxy-terminal peptide of the gamma-1 chain, which is very conserved among all laminin types, indicating that this interaction may be relevant in other tissues besides the brain. Moreover, cellular prion protein association with a peptide that mimics a putative ligand at the cell surface, p66, triggers neuroprotective signals through a cAMP/PKA-dependent pathway. Since PrPc recycles from membrane to an intracellular compartment, which is induced by copper binding, it is also possible that the internalization mechanism allows switching off elicited signals.

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