In collaboration with the Angerer lab (NIH) we examined the expression and role of GalNAc-Ts and mucin-type O-glycosylation during embryonic development of the sea urchin, S. purpuratus. One phenotype has been characterized in morphants in which SpGalNAc-T13 expression was attenuated. This results in a deficiency of embryonic skeleton and neurons, suggesting that mucin-type O-glycans play essential roles during embryonic development in S. purpuratus. Work from our laboratory challenged the hypothesis put forward by Gill et al., (The Journal of Cell Biology. 189:843, 2010) that growth factors EGF or PDGF, induce Golgi complex-to- endoplasmicreticulum (ER) relocation of both GalNAc-Ts and Tn antigen in HeLa cells,offering a mechanism for Tn antigen over-expression termed GALA. However, we were unable to reproduce these findings. Upon treatment of HeLa cells with either EGF or PDGF we observed no change in the co-localization of endogenous GalNAc-T1, GalNAc-T2 or Tn antigen with the Golgi complex marker TGN46. There was also no enhancement of localization with the ER marker calnexin. We conclude that growth factors do not cause redistribution of GalNAc-Ts from the Golgi complex to the ER in HeLa cells. Duy Tran, Gaetan Herbomel, and Jessi Becker are evaluating the targeting signals in GalNAc-Ts that direct these enzymes to the Golgi and then retain them in the Golgi. They are also using super resolution microscopy to discern which compartments in the Golgi different GalNAc-Ts are retained in. Nadine Samara and Amy Fernandez are studying the structural basis for GalNAc-T substrate specificity using X-ray crystallography. We have a collaboration with Henrik Clausen in Denmark on the role of GalNAc-T11 in early mouse development. We also have a collaboration with J.A. Kuivenhoven, in the Netherlands on GalNAc-T2 and metabolism.
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