A presynaptic endosomal trafficking pathway controls synaptic growth signaling

The Journal of Cell Biology
Avital A RodalJ Troy Littleton


Structural remodeling of synapses in response to growth signals leads to long-lasting alterations in neuronal function in many systems. Synaptic growth factor receptors alter their signaling properties during transit through the endocytic pathway, but the mechanisms controlling cargo traffic between endocytic compartments remain unclear. Nwk (Nervous Wreck) is a presynaptic F-BAR/SH3 protein that regulates synaptic growth signaling in Drosophila melanogaster. In this paper, we show that Nwk acts through a physical interaction with sorting nexin 16 (SNX16). SNX16 promotes synaptic growth signaling by activated bone morphogenic protein receptors, and live imaging in neurons reveals that SNX16-positive early endosomes undergo transient interactions with Nwk-containing recycling endosomes. We identify an alternative signal termination pathway in the absence of Snx16 that is controlled by endosomal sorting complex required for transport (ESCRT)-mediated internalization of receptors into the endosomal lumen. Our results define a presynaptic trafficking pathway mediated by SNX16, NWK, and the ESCRT complex that functions to control synaptic growth signaling at the interface between endosomal compartments.


Dec 23, 1999·Current Biology : CB·J Roos, R B Kelly
Apr 4, 2000·Current Biology : CB·M Strigini, S M Cohen
Jul 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·U FuchsA Borkhardt
May 14, 2003·The Journal of Cell Biology·Tanja WucherpfennigMarcos González-Gaitán
Jun 19, 2003·The Journal of Biological Chemistry·Brendon J Hanson, Wanjin Hong
Aug 5, 2003·The Journal of Biological Chemistry·Gabrielle E RieckhofJ Troy Littleton
Sep 17, 2003·The Journal of Cell Biology·Stephen L RogersRonald D Vale
Jul 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bénédicte FrancoYves Grau
Feb 1, 2005·Insect Biochemistry and Molecular Biology·Dennis Van HoofDick J Van der Horst
Mar 21, 2006·Current Biology : CB·Dion K DickmanThomas L Schwarz
Apr 12, 2006·The Journal of Cell Biology·Usha AcharyaJairaj K Acharya
Jun 3, 2006·Developmental Cell·Eric MaciaTomas Kirchhausen
Aug 29, 2006·Nature Reviews. Molecular Cell Biology·Juan S Bonifacino, Raul Rojas
Dec 2, 2006·International Review of Neurobiology·Guillermo Marqués, Bing Zhang
Jan 11, 2007·Journal of Microscopy·S Bolte, F P Cordelières
Sep 18, 2007·Nature Neuroscience·Sarah Huntwork, J Troy Littleton
Oct 20, 2007·The EMBO Journal·Olena PylypenkoAlexey Rak
Mar 29, 2008·Methods in Molecular Biology·Patrik VerstrekenHugo J Bellen
Jun 5, 2008·Nature Reviews. Molecular Cell Biology·Peter J Cullen
Aug 15, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Avital A RodalJ Troy Littleton
Oct 22, 2008·Experimental Cell Research·Lukasz SadowskiMarta Miaczynska
Oct 23, 2008·Structure·Qi WangHolger Sondermann
Oct 24, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Claudia MiechThomas L Schwarz
Nov 26, 2008·Molecular and Cellular Neurosciences·Yulia Akbergenova, Maria Bykhovskaia
Mar 28, 2009·Nature·Camilla Raiborg, Harald Stenmark
Apr 22, 2009·Cell·Adam FrostPietro De Camilli
Sep 17, 2009·Biochemical Society Transactions·Marcel MettlenSandra L Schmid
Oct 14, 2009·The Journal of Cell Biology·Cynthia F BarberJ Troy Littleton
Apr 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yijian RaoVolker Haucke


Feb 14, 2012·Behavior Genetics·John R ShorterGreg J Hunt
Jun 14, 2013·Molecular Biology of the Cell·Agata N BecalskaAvital A Rodal
Apr 3, 2012·The Journal of Clinical Investigation·Michael L Dustin
Jan 1, 2013·Cell Regeneration·Leilei ZhangDuanqing Pei
May 11, 2012·Journal of Cell Science·Rebecca B SmithGuillermo Marqués
Jul 11, 2013·PloS One·Phillip A VanlandinghamBing Zhang
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jihye LeeJ Troy Littleton
Dec 24, 2013·Journal of Molecular Neuroscience : MN·Gillian Muirhead, Kumlesh K Dev
Sep 15, 2012·Annual Review of Genetics·Manish JaiswalHugo J Bellen
Mar 25, 2015·The Journal of Cell Biology·Ryan J H WestSean T Sweeney
Dec 14, 2011·Current Opinion in Cell Biology·Laurel A Raftery, David M Umulis
Dec 22, 2015·Cell Reports·Charlotte F KelleyAvital A Rodal
Jun 24, 2015·Molecular and Cellular Neurosciences·Kaushiki P MenonKai Zinn
Oct 20, 2015·Communicative & Integrative Biology·Charlotte F KelleyAvital A Rodal
Sep 10, 2013·Wiley Interdisciplinary Reviews. Developmental Biology·Kaushiki P MenonKai Zinn
Mar 23, 2012·Experimental Neurobiology·Jin-A Lee, Fen-Biao Gao
Jun 2, 2016·Cell Cycle·Nathan A McDonald, Kathleen L Gould
Sep 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·Tatiana B Stanishneva-KonovalovaAvital A Rodal
Aug 19, 2016·Molecular Biology of the Cell·Mugdha DeshpandeAvital A Rodal
Nov 17, 2016·Cellular and Molecular Neurobiology·Ulrike LaugksNicole Wagner
Oct 9, 2015·Genetics·Kathryn P Harris, J Troy Littleton
Jun 28, 2015·Biologie aujourd'hui·Thomas Juan, Maximilian Fürthauer
Jun 30, 2019·The Journal of Cell Biology·ShiYu WangAvital A Rodal
Sep 26, 2018·Proceedings of the National Academy of Sciences of the United States of America·Guan-Yu XiaoSandra L Schmid
Feb 24, 2021·Cellular and Molecular Life Sciences : CMLS·Mónica C Quiñones-Frías, J Troy Littleton
May 2, 2021·Molecular Neurobiology·Neide VieiraNuno Sousa

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confocal microscopy
electron microscopy

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