The Orphan Receptor Tie1 Controls Angiogenesis and Vascular Remodeling by Differentially Regulating Tie2 in Tip and Stalk Cells

Cell Reports
Soniya SavantHellmut G Augustin

Abstract

Tie1 is a mechanistically poorly characterized endothelial cell (EC)-specific orphan receptor. Yet, Tie1 deletion is embryonic lethal and Tie1 has been implicated in critical vascular pathologies, including atherosclerosis and tumor angiogenesis. Here, we show that Tie1 does not function independently but exerts context-dependent effects on the related receptor Tie2. Tie1 was identified as an EC activation marker that is expressed during angiogenesis by a subset of angiogenic tip and remodeling stalk cells and downregulated in the adult quiescent vasculature. Functionally, Tie1 expression by angiogenic EC contributes to shaping the tip cell phenotype by negatively regulating Tie2 surface presentation. In contrast, Tie1 acts in remodeling stalk cells cooperatively to sustain Tie2 signaling. Collectively, our data support an interactive model of Tie1 and Tie2 function, in which dynamically regulated Tie1 versus Tie2 expression determines the net positive or negative effect of Tie1 on Tie2 signaling.

References

Feb 9, 2002·Genesis : the Journal of Genetics and Development·D R ShimshekR Sprengel
Feb 28, 2002·Molecular and Cellular Biology·Christopher D KontosKevin G Peters
Aug 7, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ivan B LobovRichard A Lang
Nov 1, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kristina IljinKari Alitalo
Jun 18, 2003·The Journal of Cell Biology·Holger GerhardtChrister Betsholtz
Sep 23, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Limor Chen-KonakNitzan Resnick
May 17, 2007·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hai Tao YuanS Ananth Karumanchi
Feb 17, 2009·Developmental Cell·L-K Phng, Holger Gerhardt
Feb 19, 2009·Molecular and Cellular Biology·Hai Tao YuanSamir M Parikh
Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Jul 1, 2007·Cell Adhesion & Migration·Mats HellströmHolger Gerhardt
Mar 13, 2010·Development·Xianghu QuScott Baldwin
Mar 17, 2010·Molecular Cell·Tom C M SeegarWilliam A Barton
Sep 28, 2010·Nature Cell Biology·Lars JakobssonHolger Gerhardt
Mar 9, 2011·The Journal of Clinical Investigation·Kel Vin WooH Scott Baldwin
Aug 24, 2011·Nature Reviews. Molecular Cell Biology·Shane P Herbert, Didier Y R Stainier
Sep 20, 2011·Cell·Michael PotentePeter Carmeliet
May 16, 2012·The Journal of Clinical Investigation·Moritz FelchtHellmut G Augustin
Mar 8, 2013·Cancer Research·Damien GeraldLaura E Benjamin
May 3, 2013·Cold Spring Harbor Perspectives in Biology·Lai Kuan Goh, Alexander Sorkin
Jan 17, 2014·The Journal of Clinical Investigation·Gabriela D'AmicoKari Alitalo
Mar 25, 2014·Nature Cell Biology·Katie BentleyHolger Gerhardt
Jul 8, 2015·Developmental Cell·Claudia Korn, Hellmut G Augustin

❮ Previous
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Citations

Mar 5, 2016·Cell Death and Differentiation·E C WatsonL Coultas
May 12, 2016·Annual Review of Immunology·Thomas HöferHans-Reimer Rodewald
May 12, 2005·Trends in Cardiovascular Medicine·Fumio AraiToshio Suda
Aug 23, 2016·The Journal of Clinical Investigation·Sarah B Mueller, Christopher D Kontos
Aug 23, 2016·The Journal of Clinical Investigation·Emilia A KorhonenPipsa Saharinen
May 17, 2017·Nature Communications·Do Young ParkGou Young Koh
May 23, 2017·Nature Reviews. Drug Discovery·Pipsa SaharinenKari Alitalo
Jun 25, 2017·Cellular and Molecular Life Sciences : CMLS·Emma C WatsonLeigh Coultas
Jan 23, 2018·The Journal of Clinical Investigation·Silvia La PortaHellmut G Augustin
May 5, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Tamjid A ChowdhuryRamani Ramchandran
May 4, 2017·Journal of the American Society of Nephrology : JASN·Samir M Parikh
Jan 24, 2018·Proceedings of the National Academy of Sciences of the United States of America·Tomokazu SoumaSusan E Quaggin
Aug 6, 2019·FEBS Letters·Fang-Fang HeYu-Mei Wang
Jul 10, 2019·Growth Factors·Zoe L Grant, Leigh Coultas
Jul 7, 2019·Cellular and Molecular Life Sciences : CMLS·Severin MühlederWolfgang Holnthoner
Apr 22, 2016·Science Translational Medicine·Sangyeul HanGou Young Koh
Jun 6, 2017·Current Opinion in Hematology·Samir M Parikh
Dec 13, 2016·Clinical Science·Lauri EklundPipsa Saharinen
Apr 18, 2020·EMBO Molecular Medicine·Mahak SinghalHellmut G Augustin
May 15, 2020·EMBO Molecular Medicine·Kabir A Khan, Robert S Kerbel
Sep 10, 2020·Journal of Molecular Neuroscience : MN·Yang-Yang DuanCheng Yang
May 21, 2019·Nature Metabolism·Lauren P DieboldNavdeep S Chandel
Feb 16, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tingting Su, Yasuko Iwakiri
Oct 1, 2019·Annual Review of Virology·Melissa Kane, Tatyana V Golovkina
Apr 12, 2017·Proceedings of the National Academy of Sciences of the United States of America·Veli-Matti LeppänenKari Alitalo
Apr 12, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jason O MooreKathryn M Ferguson
Oct 9, 2018·The Journal of Clinical Investigation·Seung-Jun LeeGou Young Koh
Aug 28, 2019·The Journal of Clinical Investigation·Nathalie TischCarmen Ruiz de Almodovar
Sep 19, 2017·The Journal of Clinical Investigation·Jaeryung KimGou Young Koh
Jul 19, 2017·Nature Communications·Martin TeichertHellmut G Augustin
May 22, 2019·JCI Insight·Xianghu QuH Scott Baldwin
Aug 2, 2020·Nature Communications·Bong Ihn KohInjune Kim
Jun 29, 2018·Angiogenesis·Marchien G DallingaReinier O Schlingemann
Sep 16, 2020·Development·Zhen JiangDidier Y R Stainier
Oct 7, 2020·Nature Chemical Biology·Matthew E GriffinLinda C Hsieh-Wilson
Jan 5, 2021·Inflammatory Bowel Diseases·Daniela RegensburgerElisabeth Naschberger

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Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS

Software Mentioned

Excel
GraphPad
GraphPad Prism

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