Golgi Phosphoprotein 3 Mediates the Golgi Localization and Function of Protein O-Linked Mannose β-1,2-N-Acetlyglucosaminyltransferase 1

Pereira, Natasha Ann; Pu, Helen X.; Goh, Hazel; Song, Zhiwei

doi:10.1074/jbc.m114.548305

Cited by 48 publications

(58 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are no direct interactions between the stem and catalytic domains; however, both domains contact the linker region: The interaction areas are 513.6 Å 2 for the stem domain and 925.7 Å 2 for the catalytic domain. Recently, Song's group (22) found that mislocalization of POMGnT1 to the ER occurred in clinically relevant mutations of POMGnT1: E223K, R265H, and C269Y. Our data show that all three residues are involved in the intraprotein interaction as described above.…”

Section: Resultssupporting

confidence: 58%

Carbohydrate-binding domain of the POMGnT1 stem region modulates O -mannosylation sites of α-dystroglycan

Kuwabara

Manya

Yamada

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The dystrophin glycoprotein complex, which connects the cell membrane to the basement membrane, is essential for a variety of biological events, including maintenance of muscle integrity. An O-mannose–type GalNAc-β1,3-GlcNAc-β1,4-(phosphate-6)-Man structure of α-dystroglycan (α-DG), a subunit of the complex that is anchored to the cell membrane, interacts directly with laminin in the basement membrane. Reduced glycosylation of α-DG is linked to some types of inherited muscular dystrophy; consistent with this relationship, many disease-related mutations have been detected in genes involved in O-mannosyl glycan synthesis. Defects in protein O-linked mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGnT1), a glycosyltransferase that participates in the formation of GlcNAc-β1,2-Man glycan, are causally related to muscle-eye-brain disease (MEB), a congenital muscular dystrophy, although the role of POMGnT1 in postphosphoryl modification of GalNAc-β1,3-GlcNAc-β1,4-(phosphate-6)-Man glycan remains elusive. Our crystal structures of POMGnT1 agreed with our previous results showing that the catalytic domain recognizes substrate O-mannosylated proteins via hydrophobic interactions with little sequence specificity. Unexpectedly, we found that the stem domain recognizes the β-linked GlcNAc of O-mannosyl glycan, an enzymatic product of POMGnT1. This interaction may recruit POMGnT1 to a specific site of α-DG to promote GlcNAc-β1,2-Man clustering and also may recruit other enzymes that interact with POMGnT1, e.g., fukutin, which is required for further modification of the GalNAc-β1,3-GlcNAc-β1,4-(phosphate-6)-Man glycan. On the basis of our findings, we propose a mechanism for the deficiency in postphosphoryl modification of the glycan observed in POMGnT1-KO mice and MEB patients.

show abstract

Section: Resultssupporting

confidence: 58%

Carbohydrate-binding domain of the POMGnT1 stem region modulates O -mannosylation sites of α-dystroglycan

Kuwabara

Manya

Yamada

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…It is reported that GOLPH3 interacts with and mediates the golgi localization of POMGnT1 [42], a mammalian glycosyltransferase, which promotes glioblastoma progression [43]. In addition, GOLPH3 plays an important role in integrin-mediated cell migration via the up-regulation of sialylation [8], which suggests that GOLPH3 might regulate the progression of the tumors through its biological roles of glycosylation.…”

Section: Discussionmentioning

confidence: 99%

Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

Lu¹,

Zhang²,

Fu³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Golgi phosphoprotein 3 (GOLPH3) plays pro-malignancy roles in several types of cancer. However, the molecular mechanism underlying GOLPH3 promoting tumor progression remains poorly understood. Methods: The expression of GOLPH3 and Wntless (Wls) in glioma tissues was examined by western blotting and immunohistochemistry. EdU incorporation assay and colony formation assay was used to examine the cell growth ability. The effect of GOLPH3 on Wls recycling, Wnt secretion and β-catenin activity was detected using western blotting, immunofluorescence, RT-PCR, ELISA or luciferase assay. Results: The protein levels of GOLPH3 and Wls were upregulated and positively correlated with each other in human glioma tissues. The promoting effect of GOLPH3 on glioma cell proliferation was partially mediated by Wls. In addition, GOLPH3 interacted with Wls and GOLPH3 down-regulation drove Wls into lysosome for degradation, inhibiting its recycling to golgi and the plasma membrane. Importantly, GOLPH3 down-regulation inhibited Wnt2b secretion and decreased β-catenin level and transcription activity. Conclusions: This study provides a brand new evidence that GOLPH3 promotes glioma cell proliferation by facilitating Wls recycling and Wnt/β-catenin signaling. Our findings suggest a rationale for targeting the GOLPH3-Wls-Wnt axis as a promising therapeutic approach for glioblastoma.

show abstract

“…These results are in agreement with the work of Isaji et al (42), published while our manuscript was under revision. Additionally, a recent article identified LXLRR as a putative motif for GOLPH3 recognition (27). Further work will thus be needed to define the precise consensus sequence of the GOLPH3 binding site to get a better estimation FIGURE 6.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of GOLPH3 is linked to tumor aggressiveness and poor prognosis in several human cancers (18 -25). Recent studies highlighted an interaction between GOLPH3 and coatomer (11), as well as with the cytosolic tail of the core 2 N-acetylglucosaminyltransferase 1 (C2GnT) (26) and protein O-linked mannose-1,2-Nacetlyglucosaminyltransferase 1 (27). However, evidence for a function of GOLPH3 in COPI-mediated trafficking is still missing.…”

mentioning

confidence: 99%

Golgi Phosphoprotein 3 Triggers Signal-mediated Incorporation of Glycosyltransferases into Coatomer-coated (COPI) Vesicles

Eckert

Reckmann

Hellwig

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: How Golgi phosphoprotein 3 (GOLPH3) regulates Golgi localization of glycosyltransferases in mammalian cells is poorly understood. Results: GOLPH3 mediates incorporation of glycosyltransferases into coatomer-coated vesicles. Conclusion: GOLPH3 regulates localization of glycolsyltransferases by working as a coatomer adaptor. Significance: This study provides further insight into the molecular mechanism underlying regulation of glycosyltransferases localization by GOLPH3.

show abstract

Golgi Phosphoprotein 3 Mediates the Golgi Localization and Function of Protein O-Linked Mannose β-1,2-N-Acetlyglucosaminyltransferase 1

Cited by 48 publications

References 38 publications

Carbohydrate-binding domain of the POMGnT1 stem region modulates O -mannosylation sites of α-dystroglycan

Carbohydrate-binding domain of the POMGnT1 stem region modulates O -mannosylation sites of α-dystroglycan

Golgi Phosphoprotein 3 Promotes Wls Recycling and Wnt Secretion in Glioma Progression

Golgi Phosphoprotein 3 Triggers Signal-mediated Incorporation of Glycosyltransferases into Coatomer-coated (COPI) Vesicles

Contact Info

Product

Resources

About