Heparan sulfate regulates ephrin-A3/EphA receptor signaling.

Proceedings of the National Academy of Sciences of the United States of America
Fumitoshi IrieYu Yamaguchi

Abstract

Increasing evidence indicates that many signaling pathways involve not only ligands and receptors but also various types of coreceptors and matrix components as additional layers of regulation. Signaling by Eph receptors and their ephrin ligands plays a key role in a variety of biological processes, such as axon guidance and topographic map formation, synaptic plasticity, angiogenesis, and cancer. Little is known about whether the ephrin-Eph receptor signaling system is subject to such additional layers of regulation. Here, we show that ephrin-A3 binds to heparan sulfate, and that the presence of cell surface heparan sulfate is required for the full biological activity of ephrin-A3. Among the ephrins tested, including ephrin-A1, -A2, -A5, -B1, and -B2, only ephrin-A3 binds heparin or heparan sulfate. Ephrin-A3-dependent EphA receptor activation is reduced in mutant cells that are defective in heparan sulfate synthesis, in wild-type cells from which cell surface heparan sulfate has been removed, and in the hippocampus of conditional knockout mice defective in heparan sulfate synthesis. Ephrin-A3-dependent cell rounding is impaired in CHO cells lacking heparan sulfate, and cortical neurons lacking heparan sulfate exhibit impaired...Continue Reading

References

Mar 10, 1995·The Journal of Biological Chemistry·H ShaoV M Dixit
Apr 7, 1994·Nature·T D BartleyB A Guthrie
Oct 16, 1999·Cell·T TakahashiS M Strittmatter
Aug 26, 2000·Science·M HattoriJ G Flanagan
Dec 26, 2000·The Journal of Biological Chemistry·K ShirakabeA Fujisawa-Sehara
Jul 3, 2002·Nature Reviews. Molecular Cell Biology·Klas Kullander, Rüdiger Klein
Nov 6, 2002·Biochimica Et Biophysica Acta·Beverly M ZakJeffrey D Esko
Dec 24, 2002·Nature Neuroscience·Keith K MuraiElena B Pasquale
Mar 22, 2003·Experimental Cell Research·Douglas L Falls
Oct 24, 2003·Molecular and Cellular Neurosciences·Claude SchweizerBernhard Lüscher
Dec 2, 2004·Nature Reviews. Genetics·Jeong-Soo Lee, Chi-Bin Chien
Jun 2, 2005·Nature Reviews. Molecular Cell Biology·Elena B Pasquale
Aug 3, 2005·Nature Reviews. Molecular Cell Biology·Udo HäckerNorbert Perrimon
Nov 23, 2005·Neuron·Jianhua CangDavid A Feldheim
Mar 9, 2006·Journal of Cell Science·Monique DailElena B Pasquale
Jun 30, 2006·Annual Review of Cell and Developmental Biology·Hannes E Bülow, Oliver Hobert
Aug 2, 2006·The Journal of Cell Biology·Johan KreugerUlf Lindahl
Apr 20, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yoshihiro MatsumotoYu Yamaguchi

❮ Previous
Next ❯

Citations

May 3, 2012·Cancer Metastasis Reviews·Mustapha Kandouz
Nov 21, 2013·Nature Communications·Todd LenczAriel Darvasi
Jun 11, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kazu MatsumotoYu Yamaguchi
Jan 28, 2012·The Journal of Biological Chemistry·Lei ZhouKeith K Murai
Dec 31, 2009·Development, Growth & Differentiation·Jun Takatoh, Kazunori Hanaoka
Apr 2, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Luke Truitt, Andrew Freywald
Oct 7, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Daniel FisherShuxin Li
Dec 29, 2011·Cellular and Molecular Life Sciences : CMLS·Eva NievergallPeter W Janes
Nov 27, 2010·Neurochemical Research·N MaedaK Kamimura
Nov 30, 2012·The Journal of Investigative Dermatology·Kristin GordonSpiro Getsios
Mar 31, 2011·Scandinavian Journal of Immunology·H L HolenH-C Aasheim
Oct 12, 2010·The Biochemical Journal·Halvor L HolenHans-Christian Aasheim
May 10, 2012·Cell Adhesion & Migration·Roberta NoberiniElena B Pasquale
Mar 9, 2010·Developmental Biology·Emily C GuiralMary Elizabeth Pownall
Nov 1, 2016·Journal of Neurochemistry·Masayuki Masu
Mar 8, 2018·FEBS Letters·Nancy B Schwartz, Miriam S Domowicz
Feb 13, 2018·Frontiers in Molecular Neuroscience·Giuseppe Condomitti, Joris de Wit
Jun 28, 2015·Journal of Cell Science·Nina K Thiede-Stan, Martin E Schwab
Aug 19, 2011·Glia·Keith K Murai, Elena B Pasquale
Feb 9, 2018·JCI Insight·Satoshi NozawaYu Yamaguchi
Oct 22, 2015·Development·Fabienne E Poulain, H Joseph Yost
Jun 3, 2021·International Journal of Molecular Sciences·Sampada P Mutalik, Stephanie L Gupton

❮ Previous
Next ❯

Related Concepts

Related Feeds

Axon Guidance

Axon guidance is a complex neural developmental field that investigates mechanisms through which neurons send out axons to reach its target. Here is the latest research in this domain.