Neural-specific deletion of FIP200 leads to cerebellar degeneration caused by increased neuronal death and axon degeneration.

The Journal of Biological Chemistry
Chun-Chi LiangJun-Lin Guan

Abstract

FIP200 (FAK family-interacting protein of 200 kDa) is a conserved protein recently identified as a potential mammalian counterpart of yeast autophagy protein Atg17. However, it remains unknown whether mammalian FIP200 regulates autophagy in vivo. Here we show that neural-specific deletion of FIP200 resulted in cerebellar degeneration accompanied by progressive neuronal loss, spongiosis, and neurite degeneration in the cerebellum. Furthermore, deletion of FIP200 led to increased apoptosis in cerebellum as well as accumulation of ubiquitinated protein aggregates without any deficiency in proteasome catalytic functions. We also observed an increased p62/SQSTM1 accumulation in the cerebellum and reduced autophagosome formation as well as accumulation of damaged mitochondria in the mutant mice. Lastly, analysis of cerebellar neurons in vitro showed reduced JNK activation and increased susceptibility to serum deprivation-induced apoptosis in cerebellar neurons from the mutant mice. Taken together, these results provide strong genetic evidence for a role of FIP200 in the regulation of neuronal homeostasis through its function in autophagy in vivo.

References

Sep 15, 1998·Trends in Neurosciences·D Goldowitz, K Hamre
Apr 9, 1999·Nature Neuroscience·B BatesR Jaenisch
Apr 18, 2000·The Journal of Cell Biology·H UedaJ L Guan
Jul 4, 2001·Nature Reviews. Neuroscience·V Y Wang, H Y Zoghbi
Apr 30, 2002·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
Apr 8, 2003·Trends in Biotechnology·Nigel M Hooper
Jun 6, 2003·Current Opinion in Genetics & Development·Sarah J Shoesmith Berke, Henry L Paulson
Jan 28, 2004·Cell·Cecile M Pickart
Mar 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Katerina AkassoglouMoses V Chao
Jul 24, 2004·Nature Medicine·Ella Bossy-WetzelStuart A Lipton
Dec 24, 2004·Journal of Cell Science·Daniel J Klionsky
Feb 26, 2005·Science·Gorazd B StokinLawrence S B Goldstein
Sep 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Atsushi IwataRon R Kopito
Jan 13, 2006·Nature Chemical Biology·Alexei DegterevJunying Yuan
Feb 22, 2007·Annual Review of Nutrition·Noboru Mizushima, Daniel J Klionsky
Mar 27, 2007·FEBS Letters·Kuninori Suzuki, Yoshinori Ohsumi
May 4, 2007·The EMBO Journal·Pierre-Olivier FrappartPeter J McKinnon
May 18, 2007·Annual Review of Cell and Developmental Biology·Roy V Sillitoe, Alexandra L Joyner
Jun 21, 2007·The Journal of Biological Chemistry·Serhiy PankivTerje Johansen
Aug 23, 2007·Nature Reviews. Molecular Cell Biology·Daniel J Klionsky
Nov 27, 2007·Cellular Signalling·Boyi Gan, Jun-Lin Guan
Nov 28, 2007·Annual Review of Pathology·Mondira Kundu, Craig B Thompson
Jan 5, 2008·The Journal of Biological Chemistry·Marie W WootenJorge Moscat
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
Feb 29, 2008·Nature·Noboru MizushimaDaniel J Klionsky
Apr 30, 2008·The Journal of Cell Biology·Taichi HaraNoboru Mizushima
Feb 13, 2009·Molecular Biology of the Cell·Nao HosokawaNoboru Mizushima
Feb 20, 2009·Molecular Biology of the Cell·Chang Hwa JungDo-Hyung Kim
Mar 5, 2009·The Journal of Biological Chemistry·Ian G GanleyXuejun Jiang
Jun 16, 2009·Cell·Robin MathewEileen White

❮ Previous
Next ❯

Citations

Jun 28, 2011·Cell Death and Differentiation·N Rodríguez-MuelaP Boya
Sep 3, 2010·Nature Cell Biology·Noboru Mizushima, Beth Levine
Oct 4, 2013·Nature Communications·Elmar WolfMartin Eilers
Apr 2, 2013·Nature Neuroscience·Chenran WangJun-Lin Guan
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Viviana MoresiEric N Olson
Nov 4, 2011·The Journal of Biological Chemistry·Ichiro NishimuraHidetoshi Okabe
Nov 15, 2011·Antioxidants & Redox Signaling·Edmond Y Chan
Jul 19, 2011·Genes & Development·Huijun WeiJun-Lin Guan
Apr 21, 2012·International Journal of Cell Biology·Trond Lamark, Terje Johansen
Aug 29, 2012·Future Medicinal Chemistry·Christopher W JohnsonAi Yamamoto
May 14, 2014·Annual Review of Neuroscience·Ai Yamamoto, Zhenyu Yue
Apr 18, 2013·Journal of Molecular Neuroscience : MN·Xin YuAnna-Lena Ström
Feb 19, 2010·Cellular and Molecular Life Sciences : CMLS·Gian Maria Fimia, Mauro Piacentini
Nov 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Joseph OchabaJoan S Steffan
Oct 27, 2015·Cellular and Molecular Life Sciences : CMLS·Carlo RodolfoFrancesco Cecconi
May 15, 2012·Trends in Neurosciences·Felipe A Court, Michael P Coleman
Sep 24, 2011·Ageing Research Reviews·Rita RezzaniLuigi Fabrizio Rodella
Sep 1, 2015·Experimental Eye Research·Jan Christoph Koch, Paul Lingor
May 2, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Fei LiuJun-Lin Guan
Mar 17, 2015·Molecular and Cellular Neurosciences·Constanza J Cortes, Albert R La Spada
May 16, 2013·Autophagy·Yan G ZhaoHong Zhang
Mar 15, 2013·Autophagy·Jun-Lin GuanJue Zhang
Dec 30, 2010·Autophagy·Terje Johansen, Trond Lamark
Jan 9, 2013·Autophagy·Pui-Mun WongXuejun Jiang
Oct 19, 2013·Autophagy·Aashish Joshi, Mondira Kundu
Oct 30, 2010·Current Opinion in Cell Biology·Guillermo MariñoGuido Kroemer
Mar 13, 2010·Seminars in Cell & Developmental Biology·Akiko Kuma, Noboru Mizushima
Nov 12, 2013·Progress in Neurobiology·Saeid GhavamiMarek J Łos
Nov 15, 2011·Cell·Noboru Mizushima, Masaaki Komatsu
Sep 3, 2011·Cell·David C RubinszteinGuido Kroemer
Nov 5, 2014·Acta Neuropathologica·Markus DammeEeva-Liisa Eskelinen
Jun 6, 2012·International Journal of Cell Biology·Fulvio ReggioriAnne Simonsen
Dec 20, 2014·Cell Death and Differentiation·V NikoletopoulouN Tavernarakis
Dec 19, 2013·International Journal of Cell Biology·Karina Cuanalo-ContrerasClaudio Soto
Apr 4, 2017·FEBS Letters·Kaori TakayamaEisuke Itakura

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

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

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

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.