Genetic variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfate diversity.

Heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans (PG) consist of a core protein to which the glycosaminoglycan (GAG) chains, HS or CS, are attached through a common linker tetrasaccharide. In the extracellular space, they are involved in the regulation of cell communication, assuring development and homeostasis. The HSPG biosynthetic pathway has documented 51 genes, with many diseases associated to defects in some of them.

HS3ST2 expression induces the cell autonomous aggregation of tau.

Heparan sulfates have long been known to intracellularly accumulate in Alzheimer's disease neurons, where they colocalize with neurofibrillary tangles made of abnormally phosphorylated and aggregated tau protein. However, the reasons and consequences of the heparan sulfates accumulation in the Alzheimer's cells are not yet well understood. Previously, we showed that the neural heparan sulfate 3-O-sulfotransferase HS3ST2 is critical for the abnormal phosphorylation of tau in Alzheimer's disease-related tauopathy.

Expression Dynamics of the -Glycosylated Proteins Recognized by Lectin in T Lymphocytes and Its Relationship With Moesin as an Alternative Mechanism of Cell Activation.

T lymphocyte activation begins with antigen/MHC recognition by the TCR/CD3 complex followed by a costimulatory signal provided by CD28. The search for novel costimulatory molecules has been extensive due to their potential use as immunotherapeutic targets. Although some molecules have been identified, they are unable to provide sustainable signaling to allow for proper T cell activation and proliferation.

Relevance of glycans in the interaction between T lymphocyte and the antigen presenting cell.

The immunological synapse promotes receptors and ligands interaction in the contact interface between the T lymphocyte and the antigen presenting cell; glycosylation of the proteins involved in this biological process favors regulation of molecular interactions and development of the T lymphocyte effector response. Glycans in the immunological synapse influence cellular and molecular processes such as folding, expression, and structural stability of proteins, they also mediate ligand-receptor interaction and propagation of the intracellular signaling or inhibition of uncontrolled cellular activation that could lead to the development of autoimmunity, among others. It has been suggested that altered glycosylation of proteins that participate in the immunological synapse affects the signaling processes and cell proliferation, as well as exacerbation of the effector mechanisms of T cells that trigger systemic damage and autoimmunity.