CHEMICAL BIOLOGY : A little sugar for the brain

The amount of sugar on proteins inside neural cells changes in response to brain stimulation, which implicates sugar modification as a new player in brain signalling, according to a paper to be published in the June issue of Nature Chemical Biology. Changes in the levels of phosphorylation of serine and threonine residues have a well-known role in cell signalling. Although most glycosylation, or modification of proteins by the attachment of sugars, occurs on proteins outside the cell, one sugar modification, called O-GlcNAc, can be attached to serine or threonine residues of proteins inside cells. Because phosphorylation and O-GlcNAc modifications occur on exactly the same amino acid side chains, O-GlcNAc could be critical in cellular signalling. However, a lack of tools to identify the precise positions of O-GlcNAc modifications in vivo has made it difficult to investigate this hypothesis.
Linda Hsieh-Wilson and colleagues have now developed a proteomic method that uses mass spectrometry to determine in vivo O-GlcNAc levels. When rats were injected with an excitatory stimulus, the authors identified changes in the sugar levels at specific sites of proteins found in the brain. With this information, it will now be possible to investigate the exact role O-GlcNAc plays in brain function.
Author contact:
Linda Hsieh-Wilson (California Institute of Technology, Pasadena, CA, USA)
Tel: +1 626 395 6101; E-mail: lhw@caltech.edu