Roles of autophagy and mTOR signaling in neuronal differentiation of mouse neuroblastoma cells

Cellular Signalling
Mei Zeng, Jiang-Ning Zhou

Abstract

Cell differentiation is often associated with decreased cell growth, indicating an altered rate of macromolecule synthesis and degradation. In this study, we present evidence that autophagy, a process for bulk degradation of cytoplasm, is activated during retinoic acid-induced neuronal differentiation of neuroblastoma N2a cells. Chemical inhibitors of autophagy, including 3-MA and LY294002, abrogate cell differentiation. RNA interference of autophagy gene beclin 1 markedly delays the process of differentiation. We also find that cell differentiation is accompanied by decreased activity of mTOR, a major controller of cell growth and a negative regulator of autophagy. However, completely inhibiting mTOR by rapamycin decreases neurite outgrowth, cell size and the immunoreactivity for neuronal markers. Our study suggests that an appropriate level of mTOR activity is important in cell differentiation for a balance between macromolecule synthesis and degradation.

References

Mar 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·P O Seglen, P B Gordon
Mar 28, 1998·The Journal of Biological Chemistry·T Noda, Y Ohsumi
Jan 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shao Jun TangErin M Schuman
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Aug 13, 2002·Nature Cell Biology·Christopher J PotterTian Xu
Aug 21, 2002·The Journal of Cell Biology·Rita GalloAlberto Gulino
May 20, 2003·FEBS Letters·Gábor JuhászMiklós Sass
Nov 19, 2003·Proceedings of the National Academy of Sciences of the United States of America·Maurizio CammalleriPietro Paolo Sanna
Dec 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Zhenyu YueNathaniel Heintz
Jan 20, 2004·Trends in Biochemical Sciences·Yong LiKun-Liang Guan
Jan 23, 2004·The Journal of Biological Chemistry·Grant P OttoRichard H Kessin
Apr 8, 2004·Developmental Cell·Beth Levine, Daniel J Klionsky
Aug 7, 2004·Developmental Cell·Ryan C ScottThomas P Neufeld
Nov 5, 2004·Nature·Akiko KumaNoboru Mizushima
Apr 28, 2005·Current Biology : CB·Xiaomeng LongJoseph Avruch
May 4, 2005·The Journal of Cell Biology·Masaaki KomatsuTomoki Chiba
Jun 2, 2005·Nature Reviews. Molecular Cell Biology·Julian J LumCraig B Thompson
Aug 23, 2005·Current Biology : CB·Krisztina Takacs-VellaiFritz Müller
Nov 16, 2005·Nature Neuroscience·Sohail F TavazoieBernardo L Sabatini
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall

❮ Previous
Next ❯

Citations

Jun 7, 2012·Cellular and Molecular Life Sciences : CMLS·Kanchan PhadwalAnna Katharina Simon
Sep 14, 2011·Cell Research·Ellen WirawanPeter Vandenabeele
Mar 13, 2009·The Journal of Biological Chemistry·Peter O BauerNobuyuki Nukina
Oct 13, 2011·Journal of Molecular Cell Biology·Kangkai WangPappachan E Kolattukudy
Apr 23, 2014·PloS One·Bettina ThauererGabriele Baier-Bitterlich
Jan 22, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cristina MalageladaLloyd A Greene
Oct 1, 2011·Chinese Journal of Cancer·Wen-Zhuo ZhuangZhong-Qin Liang
Apr 9, 2013·Neurochemical Research·Kangyong LiuXiaojiang Sun
Feb 26, 2016·Stem Cell Reports·Mengtao LiYun Bai
Dec 17, 2015·Histochemistry and Cell Biology·Mohammed ArastooAlan J Stewart
Apr 12, 2015·Developmental Biology·Elizabeth StewartMichael A Dyer
Oct 27, 2015·Cellular and Molecular Life Sciences : CMLS·Carlo RodolfoFrancesco Cecconi
Feb 13, 2010·The American Journal of Pathology·Latika Kohli, Kevin A Roth
Dec 17, 2009·Brain Research·Yaodong ZhaoTianyi Zhang
Apr 18, 2012·Journal of Neuropathology and Experimental Neurology·Krystyna BajsarowiczStephen J DeArmond
May 25, 2013·Journal of Biochemical and Molecular Toxicology·Ye ChenJiamei Liu
Dec 15, 2012·Journal of Neurochemistry·Petra PopovicsAlan J Stewart
May 29, 2014·The Biochemical Journal·Elliott M McMillan, Joe Quadrilatero
Nov 27, 2014·Cancer Chemotherapy and Pharmacology·Yi-Hui LinPei-Ming Chu
Mar 15, 2013·Autophagy·Jun-Lin GuanJue Zhang
Apr 14, 2015·Scientific Reports·Isabelle HatfieldDave Bridges
May 31, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chang ChenLiangren Zhang
Nov 8, 2017·Asian Pacific Journal of Tropical Medicine·Jun-Chao FanDao-Xian Hong
Aug 31, 2018·FEMS Yeast Research·Xinchen TengJ Marie Hardwick

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms