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  current news   Press   selected story    
     
  4th June 2010  
 

Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes.

 
 




Author
David Gill1, Joanne Chia1, Jamie Senewiratne1 and Frederic Bard1,2

Affiliations:
1 – Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673
2 – National University of Singapore, 21 Lower Kent Ridge Road, Singapore 119077

Published in J Cell Biol. 2010 May 24. [Epub ahead of print]

Abstract
Following growth factor stimulation, kinases are activated to regulate multiple aspects of cell physiology. Activated Src is present on Golgi membranes but its function here remains unclear. We find that Src regulates mucin-type protein O-glycosylation through redistribution of the initiating enzymes, polypeptide N-acetylgalactosaminyl transferases (GalNac-Ts), from the Golgi to the ER. Redistribution occurs after stimulation with EGF or PDGF in a Src dependent manner and in cells with constitutively elevated Src activity. All GalNac-T family enzymes tested are affected whereas multiple other glycosylation enzymes are not displaced from the Golgi. Upon Src activation, the COP-I coat is also redistributed in punctate structures that co-localize with GalNac-Ts and a dominant negative Arf1 isoform, Arf1(Q71L), efficiently blocks GalNac-Ts redistribution, indicating that Src activates a COP-I dependent trafficking event. Finally, Src activation increases O-glycosylation initiation as seen by lectin staining and metabolic labeling. We propose that growth factor stimulation regulates O-glycosylation initiation in a Src dependent fashion by GalNac-Ts redistribution to the ER.

 
 

 
 


Title: Effect of growth factors on the Golgi.
Legend: Treatment of cells with EGF results in the redistribution of O-glycosylation enzymes (in green) from the Golgi (in red) to the ER and ERGIC compartments. Left hand cell: EGF stimulated cell; Right hand cell: control cell. Blue: DNA, green: Helix Pomatia Lectin (O-glycosylation marker), red: Giantin (Golgi marker). Redistribution of the enzymes results in an increase of their activity.

For more information on Frederic Bardís laboratory, please click here.