Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Brian A PierchalaEugene M Johnson

Abstract

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, ...Continue Reading

Citations

Jan 19, 2013·Apoptosis : an International Journal on Programmed Cell Death·Minakshi MazumdarTanya Das
Oct 13, 2006·Pituitary·Yoshiki MurakumoMasahide Takahashi
Oct 6, 2007·Endocrine Pathology·Andrea Z LaiLois M Mulligan
Jul 27, 2010·Proceedings of the National Academy of Sciences of the United States of America·Moses V Chao
Aug 10, 2012·Molecular Biology of the Cell·Douglas S RichardsonLois M Mulligan
May 6, 2010·Human Molecular Genetics·Daniela FuscoGiovanni Romeo
Jan 28, 2014·PloS One·Stephen C KalesStanley Lipkowitz
Aug 30, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cynthia C Tsui, Brian A Pierchala
Apr 16, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cynthia C Tsui, Brian A Pierchala
Dec 24, 2013·Chemistry and Physics of Lipids·Olga S OstroumovaLudmila V Schagina
Dec 24, 2013·Molecular Neurobiology·Sandro SonninoAlessandro Prinetti
Sep 6, 2013·Cell Communication & Adhesion·Panagiotis J VlachostergiosChristos N Papandreou
Oct 16, 2007·Annals of Medicine·Pia Runeberg-Roos, Mart Saarma
Apr 30, 2014·Journal of Cellular Physiology·Marta RusminiIsabella Ceccherini
Mar 30, 2010·Journal of Chemical Neuroanatomy·Phalguni Anand AlladiUday Muthane
Jan 13, 2009·Pharmacology & Therapeutics·Sebastien Carnicella, Dorit Ron
Jul 4, 2008·Trends in Neurosciences·Gustavo Paratcha, Fernanda Ledda
Jan 24, 2007·Journal of Neurochemistry·Brian A PierchalaEugene M Johnson
Mar 22, 2008·The FEBS Journal·T K LundgrenPatrik Ernfors
Mar 22, 2016·Developmental Biology·Robert O Heuckeroth, Karl-Herbert Schäfer
Sep 11, 2007·Biophysical Journal·Jihong TongThomas J McIntosh
Oct 12, 2015·The Journal of Membrane Biology·Svetlana S EfimovaOlga S Ostroumova
May 11, 2007·Biochemical and Biophysical Research Communications·Alda TufroGuillermo Villegas
Apr 27, 2012·Neurobiology of Aging·Diana ScholzMarcel Leist
May 15, 2013·Journal of Neuroscience Methods·Luís QuintinoCecilia Lundberg
Apr 11, 2017·Traffic·Eitan Erez ZahaviEran Perlson
Aug 11, 2011·Journal of Dental Research·Z GaleB A A Scheven
Feb 25, 2014·Nature Reviews. Cancer·Lois M Mulligan
Aug 11, 2017·Journal of Cell Science·Brandy D HyndmanLois M Mulligan
Jan 15, 2008·Journal of Cellular Biochemistry·T Kalle LundgrenPatrik Ernfors
Jan 15, 2015·American Journal of Physiology. Renal Physiology·Guoqing HouCynthia C Tsui

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.