Pofut1 point-mutations that disrupt O-fucosyltransferase activity destabilize the protein and abolish Notch1 signaling during mouse somitogenesis

PloS One
Rieko AjimaYumiko Saga

Abstract

The segmental pattern of the vertebrate body is established via the periodic formation of somites from the presomitic mesoderm (PSM). This periodical process is controlled by the cyclic and synchronized activation of Notch signaling in the PSM. Protein O-fucosyltransferase1 (Pofut1), which transfers O-fucose to the EGF domains of the Notch1 receptor, is indispensable for Notch signaling activation. The Drosophila homologue Ofut1 was reported to control Notch localization via two different mechanisms, working as a chaperone for Notch or as a regulator of Notch endocytosis. However, these were found to be independent of O-fucosyltransferase activity because the phenotypes were rescued by Ofut1 mutants lacking O-fucosyltransferase activity. Pofut1 may also be involved in the Notch receptor localization in mice. However, the contribution of enzymatic activity of Pofut1 to the Notch receptor dynamics remains to be elucidated. In order to clarify the importance of the O-fucosyltransferase activity of Pofut1 for Notch signaling activation and the protein localization in the PSM, we established mice carrying point mutations at the 245th a.a. or 370-372th a.a., highly conserved amino-acid sequences whose mutations disrupt the O-fucosylt...Continue Reading

References

Jul 1, 1997·The EMBO Journal·H AberleR Kemler
May 30, 1998·Journal of Biochemistry·C BretonA Imberty
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·C A Wiggins, S Munro
Aug 10, 2000·Nature·D J MoloneyT F Vogt
Jan 5, 2002·The Journal of Biological Chemistry·Birgit M JehnWolfgang Bielke
May 31, 2002·The Journal of Biological Chemistry·Vladislav M PaninRobert S Haltiwanger
Jan 16, 2003·Cell·Tetsuya Okajima, Kenneth D Irvine
Apr 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Shaolin Shi, Pamela Stanley
Aug 12, 2003·The Journal of Biological Chemistry·Tetsuya OkajimaKenneth D Irvine
Oct 23, 2003·Nature Reviews. Molecular Cell Biology·Nicola Haines, Kenneth D Irvine
Jan 18, 2005·The Journal of Biological Chemistry·Yi Luo, Robert S Haltiwanger
Feb 21, 2006·Current Opinion in Cell Biology·Roland Le Borgne
Jun 23, 2007·Current Molecular Medicine·Raajit RampalRobert S Haltiwanger
Jan 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Changhui Ge, Pamela Stanley
Mar 19, 2008·The Journal of Biological Chemistry·Mark StahlPamela Stanley
Jun 13, 2008·Mechanisms of Development·Yoshiaki Okamura, Yumiko Saga
May 7, 2009·Traffic·Maximilian Fürthauer, Marcos González-Gaitán
Sep 8, 2010·Current Topics in Developmental Biology·Pamela Stanley, Tetsuya Okajima
Sep 8, 2010·Current Topics in Developmental Biology·Shinya YamamotoHugo J Bellen
Sep 8, 2010·Current Topics in Developmental Biology·Ellen Jorissen, Bart De Strooper
Oct 30, 2010·Traffic·Stéphanie Le BrasRoland Le Borgne
Jan 27, 2011·Methods in Enzymology·Christine M Oslowski, Fumihiko Urano
Aug 31, 2011·Cold Spring Harbor Perspectives in Biology·Kazutaka Araki, Kazuhiro Nagata
Oct 4, 2011·PloS One·Erandi Lira-NavarreteRamon Hurtado-Guerrero
Feb 7, 2012·Seminars in Cell & Developmental Biology·Abdiwahab A MusseGerry Weinmaster
Jun 30, 2012·Current Opinion in Genetics & Development·Yumiko Saga
Jun 30, 2012·Science·Martin JinekEmmanuelle Charpentier
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 31, 2013·Nature Biotechnology·Wenyan JiangLuciano A Marraffini
Mar 23, 2013·International Journal of Molecular Sciences·Julien Moretti, Christel Brou
Jul 23, 2013·Nature Biotechnology·Patrick D HsuFeng Zhang
Jun 10, 2014·Biochemical and Biophysical Research Communications·Hideyuki Takeuchi, Robert S Haltiwanger
Oct 23, 2014·Nature Reviews. Molecular Cell Biology·Alexis Hubaud, Olivier Pourquié
Feb 24, 2015·Science·Vincent C LucaK Christopher Garcia

❮ Previous
Next ❯

Citations

Sep 13, 2018·FEBS Letters·Shweta Varshney, Pamela Stanley
Jun 7, 2019·Journal of Cutaneous Medicine and Surgery·Abdulhadi H JfriElena Netchiporouk
Jul 8, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Andy MadridBermans J Iskandar
Nov 2, 2018·Cancers·Julien ChabanaisAbderrahman Maftah
Dec 21, 2020·Molecular Aspects of Medicine·Kenjiroo MatsumotoRobert S Haltiwanger

❮ Previous
Next ❯

Methods Mentioned

BETA
glycosylation
confocal microscopy
PCR
in vitro transcription
Seq
Protein Assay
transfection
genotyping
transmission electron microscopy
targeted mutations

Software Mentioned

ImageJ
Protein 3D modeling
Phyre2

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.