Rufy3 is an adapter protein for small GTPases that activates a Rac guanine nucleotide exchange factor to control neuronal polarity

The Journal of Biological Chemistry
Atsuko HondaMichihiro Igarashi

Abstract

RUN and FYVE domain-containing 3 (Rufy3) is an adapter protein for small GTPase proteins and is bound to activated Rap2, a Ras family protein in the developing neuron. Previously, we reported the presence of a rapid cell polarity determination mechanism involving Rufy3, which is likely required for in vivo neuronal development. However, the molecular details of this mechanism are unclear. To this end, here we produced Rufy3 knock-out (Rufy3-KO) mice to study the role of Rufy3 in more detail. Examining Rufy3-KO neurons, we found that Rufy3 is recruited via glycoprotein M6A to detergent-resistant membrane domains, which are biochemically similar to lipid rafts. We also clarified that Rufy3, as a component of a ternary complex, induces the assembly of Rap2 in the axonal growth cone, whereas in the absence of Rufy3, the accumulation of a Rac guanine nucleotide exchange factor, T-cell lymphoma invasion and metastasis 2 (Tiam2/STEF), is inhibited downstream of Rap2. We also found that Rufy3 regulates the cellular localization of Rap2 and Tiam2/STEF. Taken together, we conclude that Rufy3 is a physiological adapter for Rap2 and activates Tiam2/STEF in glycoprotein M6A-regulated neuronal polarity and axon growth.

References

Jun 5, 1997·Nature·K Simons, E Ikonen
Apr 2, 1998·European Journal of Biochemistry·I Janoueix-LeroseyJ de Gunzburg
Nov 15, 2001·The Journal of Biological Chemistry·Naoki MatsuoYo-ichi Nabeshima
May 18, 2004·Biochemical and Biophysical Research Communications·Toshimitsu FuseMasayoshi Mishina
Feb 22, 2005·Nature Cell Biology·Takashi NishimuraKozo Kaibuchi
Jun 28, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yuki MiyamotoWilliam C Mobley
Aug 25, 2006·The Journal of Biological Chemistry·Mutsuko Kukimoto-NiinoShigeyuki Yokoyama
Feb 15, 2007·Neuroscience Research·Masayoshi Mishina, Kenji Sakimura
Apr 19, 2007·The Journal of Biological Chemistry·Tatsuya MoriNaoyuki Inagaki
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Motohiro NozumiMichihiro Igarashi
Jun 26, 2012·Current Opinion in Cell Biology·Alfredo CáceresCarlos G Dotti
Sep 14, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hitomi NakazawaNaoyuki Inagaki
Mar 23, 2013·International Journal of Molecular Sciences·Yasuko Kitagishi, Satoru Matsuda
Jul 30, 2014·Neuroscience Research·Michihiro Igarashi
Oct 24, 2014·Frontiers in Cellular Neuroscience·Trisha R Stankiewicz, Daniel A Linseman
Jul 3, 2015·Physiological Reviews·Takashi NambaKozo Kaibuchi
Oct 17, 2015·Angewandte Chemie·Philipp M CrommHerbert Waldmann
Apr 29, 2016·Cytoskeleton·David Villarroel-CamposChristian Gonzalez-Billault
May 18, 2016·Biological Chemistry·Bhavin Shah, Andreas W Püschel
Mar 10, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Atsuko HondaMichihiro Igarashi

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Citations

Sep 25, 2019·Journal of Experimental & Clinical Cancer Research : CR·Huiqiong ZhuJide Wang
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Rémy Char, Philippe Pierre
Sep 15, 2020·Frontiers in Molecular Neuroscience·Michihiro IgarashiMotohiro Nozumi
Nov 18, 2020·Biochemical Society Transactions·Joe MaltasAngeliki Malliri
Apr 12, 2020·Journal of Neuroscience Methods·Michihiro IgarashiShujiro Okuda
Jun 22, 2019·Neuron·Nicholas T HertzMarc Tessier-Lavigne

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