The IgLON Family Member Negr1 Promotes Neuronal Arborization Acting as Soluble Factor via FGFR2

Frontiers in Molecular Neuroscience
Francesca Pischedda, Giovanni Piccoli

Abstract

IgLON proteins are GPI anchored adhesion molecules that control neurite outgrowth. In particular, Negr1 down-regulation negatively influences neuronal arborization in vitro and in vivo. In the present study, we found that the metalloprotease ADAM10 releases Negr1 from neuronal membrane. Ectodomain shedding influences several neuronal mechanisms, including survival, synaptogenesis, and the formation of neurite trees. By combining morphological analysis and virus-mediated selective protein silencing in primary murine cortical neurons, we found that pharmacologically inhibition of ADAM10 results in an impairment of neurite tree maturation that can be rescued upon treatment with soluble Negr1. Furthermore, we report that released Negr1 influences neurite outgrowth in a P-ERK1/2 and FGFR2 dependent manner. Together our findings suggest a role for Negr1 in regulating neurite outgrowth through the modulation of FGFR2 signaling pathway. Given the physiological and pathological role of ADAM10, Negr1, and FGFR2, the regulation of Negr1 shedding may play a crucial role in sustaining brain function and development.

References

Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·S LammichF Fahrenholz
Nov 14, 2001·The Journal of Cell Biology·S MechtersheimerP Altevogt
Mar 23, 2005·The Journal of Cell Biology·Alka MansukhaniClaudio Basilico
Jun 11, 2005·Molecular and Cellular Neurosciences·Michael SchäferThomas Brümmendorf
Jul 28, 2005·Journal of Neurochemistry·Vladislav V KiselyovElisabeth Bock
Nov 10, 2005·Journal of Neurochemistry·Simone DiestelPatricia F Maness
Dec 20, 2005·Current Opinion in Neurobiology·Tomoko Tada, Morgan Sheng
May 23, 2006·Nature Neuroscience·Karen Müller SmithFlora M Vaccarino
Sep 13, 2006·Journal of Neurobiology·C Leann HinklePatricia F Maness
Oct 13, 2006·Progress in Neurobiology·Luca Bonfanti
Jul 12, 2007·Journal of Proteome Research·Giovanni PiccoliCarlo Sala
Nov 6, 2007·Frontiers in Bioscience : a Journal and Virtual Library·Corinna Haupt, Andrea B Huber
Nov 29, 2007·Journal of Cell Science·Chiara FrancavillaUgo Cavallaro
Oct 3, 2008·The American Journal of Psychiatry·Elizabeth G HollidayBryan J Mowry
Oct 14, 2008·Journal of Autism and Developmental Disorders·Flora M VaccarinoHanna E Stevens
Apr 24, 2009·The Journal of Investigative Dermatology·Masaru Katoh
Jun 23, 2009·Methods in Molecular Biology·Christian Johannes GloecknerMarius Ueffing
Aug 28, 2009·Cell Biochemistry and Function·Takashi HashimotoSeiji Miyata
Nov 28, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Barbara HausottLars Klimaschewski
Dec 30, 2009·The Journal of Cell Biology·Chiara FrancavillaUgo Cavallaro
Apr 8, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ellen JorissenPaul Saftig
Apr 23, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hanna E StevensFlora M Vaccarino
Jul 2, 2010·Cold Spring Harbor Perspectives in Biology·Jonathan Raper, Carol Mason
Jan 21, 2011·Molecular Autism·John P HussmanMargaret A Pericak-Vance
Feb 14, 2013·Nature Reviews. Molecular Cell Biology·Regina Goetz, Moosa Mohammadi
Feb 22, 2013·Autism Research : Official Journal of the International Society for Autism Research·Mehmet Akif CoskunBhavin R Sheth
Aug 22, 2013·Journal of Psychiatric Research·Giuseppina MaccarroneChristoph W Turck

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Citations

Feb 27, 2018·Frontiers in Molecular Neuroscience·Katyayani SinghMichael K E Schäfer
Nov 27, 2018·F1000Research·Shalini Menon, Stephanie Gupton
Feb 26, 2019·Nature Genetics·Jakob GroveAnders D Børglum
Mar 28, 2020·Molecular Psychiatry·Shiwu LiXiong-Jian Luo
Apr 7, 2018·Frontiers in Cellular Neuroscience·Francesca PischeddaGiovanni Piccoli
Dec 8, 2020·Frontiers in Molecular Neuroscience·Irina KozlovaVladimir Sytnyk
Oct 3, 2021·Scientific Reports·Sydney FearnleyJean-François Cloutier
May 26, 2018·Science Translational Medicine·Gunnar H D PoplawskiMark H Tuszynski

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Methods Mentioned

BETA
transfection
immunoprecipitation
confocal microscopy

Software Mentioned

NeuronStudio
ImageJ

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