Tankyrase-1-mediated degradation of Golgin45 regulates glycosyltransferase trafficking and protein glycosylation in Rab2-GTP-dependent manner

Xihua Yue,Intaek Lee,Hai Dang Truong Ngo,Bopil Gim,Neeraj Tiwari,Lianhui Zhu,Jae-Min Lim,Yijing Wang,Yi Qian,Shuaiyang Jing

doi:10.1038/s42003-021-02899-0

Abstract

Altered glycosylation plays an important role during development and is also a hallmark of increased tumorigenicity and metastatic potentials of several cancers. We report here that Tankyrase-1 (TNKS1) controls protein glycosylation by Poly-ADP-ribosylation (PARylation) of a Golgi structural protein, Golgin45, at the Golgi. TNKS1 is a Golgi-localized peripheral membrane protein that plays various roles throughout the cell, ranging from telomere maintenance to Glut4 trafficking. Our study indicates that TNKS1 localization to the Golgi apparatus is mediated by Golgin45. TNKS1-dependent control of Golgin45 protein stability influences protein glycosylation, as shown by Glycomic analysis. Further, FRAP experiments indicated that Golgin45 protein level modulates Golgi glycosyltransferease trafficking in Rab2-GTP-dependent manner. Taken together, these results suggest that TNKS1-dependent regulation of Golgin45 may provide a molecular underpinning for altered glycosylation at the Golgi during development or oncogenic transformation.

Highlights

Altered glycosylation plays an important role during development and is a hallmark of increased tumorigenicity and metastatic potentials of several cancers
In order to determine how much of these altered protein glycosylation may be attributed to regulation of Golgin[45] protein stability by TNKS1, we studied whether XAV939 treatment in Golgin[45] knockdown cells fails to induce a similar change in protein glycosylation, compared to XAV939 treatment alone
Studies have already shown that Wnt/β-catenin signaling directly targets and regulates DPAGT1 gene, the dolichol-P-dependent Nacetylglucosamine-1-phosphate-transferase (GPT), which initiates the synthesis of the lipid-linked oligosaccharide precursor for protein N-glycosylation in the endoplasmic reticulum[34,35,36]

Summary

Introduction

Altered glycosylation plays an important role during development and is a hallmark of increased tumorigenicity and metastatic potentials of several cancers. FRAP of β(1, 4)-galactosyltransferase fused to GFP (GalT1-GFP), a Golgi glycosyltransferease, and Glycomic analysis by mass spectrometry indicated that Golgin[45] protein stability drastically influences protein glycosylation by regulating glycosyltransferase trafficking dynamics in a Rab2-GTP-dependent manner. These results suggest that TNKS1 activity is closely associated with modulation of Golgi function to a previously unanticipated degree and may greatly influence protein glycosylation at the Golgi during development or oncogenic transformation

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