Glycans that regulate development and notch signaling

Glycans that regulate development and notch signaling Air date: Wednesday, May 06, 2015, 3:00:00 PM Category: WALS - Wednesday Afternoon Lectures Runtime: 01:04:03 Description: NIH Wednesday Afternoon Lecture Notch signaling occurs when cell surface Notch receptors are stimulated by Notch ligands on an apposing cell. This interaction leads to release of the Notch receptor intracellular domain which complexes with several factors in the nucleus to induce the expression of Notch target genes. A large variety of cell fate decisions depend on regulated Notch signaling during development and differentiation in mammals. Thus, several human diseases and cancers arise from the malfunctioning of Notch signaling pathways. Diseases range from skeletal deformities to heart disease to a variety of cancers. The O-fucose glycans attached to the extracellular domain of Notch receptors play critical but ill-defined roles in the regulation of Notch signaling. In their absence, mouse embryos die at mid-gestation with defects typical of a loss of signaling through all four Notch receptors. O-fucose on Notch receptors is elongated by the addition of another sugar GlcNAc by one of three Fringe GlcNAc-transferases. Dysregulation of Notch signaling by altered glycosyltransferase gene expression has been associated with developmental defects and cancer prognosis. The Stanley laboratory is working to understand molecular mechanisms by which O-fucose glycans and the different Fringe activities regulate Notch signaling. A particular challenge is that there are three Fringe genes, often expressed together in a given tissue. Stanley's lab has used genetic strategies to generate cultured cells and mice with Notch receptors that carry no fucose, or only O-fucose, or O-fucose with GlcNAc transferred by a single Fringe enzyme, to identify roles for O-fucose and each Fringe glycosyltransferase in embryonic development and in T and B cell development. For more information go to https://oir.nih.gov/wals Author: Pamela Stanley, Ph.D., Albert Einstein College Medicine Permanent link: http://videocast.nih.gov/launch.asp?18983