Joanne Chia1,2,, Germaine Goh1, Victor Racine1, Susanne Ng1, Pankaj Kumar1 and Frederic Bard1,2.
1- Institute of Molecular and Cell Biology, Singapore .
2- National University of Singapore, Singapore.
Published in Molecular Systems Biology on 4th Dec 2012
To read the paper, please click here.
Glycans are complex sugar molecules present at the surface of cells. As they are involved in most cell-cell interactions in the body, they impact numerous human physiological functions, including the fertilization of the egg, multiple developmental processes, immune responses and diseases such as cancer. Glycans represent a large and diverse family of molecules whose expression varies depending on cell type and cell status. However, the basis for the regulation of their expression is mostly unknown. Glycans are mostly synthesized in the Golgi apparatus, an intricate membranous organelle snugged next to the nucleus. Recently, we proposed that a signaling cascade can impact the organization of the Golgi apparatus and regulate the synthesis of a particular glycan. In this study, we systematically probed signaling genes by RNA interference and found that over a 100 different signaling molecules can also impact the organization of the Golgi apparatus and regulate the expression of various glycans. Our study uncovers how surprisingly extended is the range of interactions between signaling pathways and glycosylation pathways. It represents a new basis to unravel how cells modulate their sugar coats to adapt and respond to signals and changes in the body.
Figure Legend: RNAi screening and automated image analysis reveal 180 kinases and phosphatases regulating the organization of the Golgi apparatus. Most of these genes also control the expression of specific glycans, pointing to a web of interactions between signaling cascades and glycosylation at the Golgi.
Golgi organization was probed with three markers of different Golgi compartments and quantitative morphological analysis.
Knockdowns of ~20% of all known kinases and phosphatases affected the Golgi globally or in a compartment-specific manner, and were comparable in degree to the depletion of known membrane traffic regulators such as SNAREs.
Several cell surface receptors, their cognate ligands and downstream effectors regulate Golgi organization, suggesting a large regulatory network.
Most signaling genes affected both Golgi morphology and the expression of specific glycans.
For more information on Frederic BARD’s laboratory, please click here.