Electronic Theses and Dissertations

Deepthi Raghu

Date

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Biology

Committee Chair

Amy Abell

Committee Member

Judith Cole

Committee Member

Omar Skalli

Committee Member

Ramin Homayouni

Abstract

O-GalNAc glycosylation is initiated in the Golgi by glycosyltransferases called GALNTs. Proteomic screens identified >600 O-GalNAc modified proteins, but biological relevance of these modifications has been difficult to determine. We have discovered a conserved function for GALNT3 in trophoblast stem (TS) cells, blastocyst trophectoderm, and human mammary epithelial cells (HMECs). Loss of GALNT3 expression in these systems reduces O-GalNAc glycosylation and induces epithelial-mesenchymal transition. Further, Galnt3 expression is reduced in aggressive, mesenchymal Claudin-low breast cancer cells. We show that GALNT3 expression controls the O-GalNAc glycosylation of multiple proteins including E-cadherin in both TS cells and HMECs. Loss of GALNT3 results in the intracellular retention of E-cadherin in the Golgi. Significantly, re-expression of GALNT3 in TS cells increases O-GalNAc glycosylation and restores the epithelial state. Together, these data demonstrate the critical biological role of GALNT3 O-GalNAc glycosylation to promote the epithelial phenotype in TS cells, blastocyst trophectoderm, and HMECs.

Comments

Data is provided by the student.

Library Comment

Dissertation or thesis originally submitted to ProQuest

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