LMTK1/AATYK1 is a novel regulator of axonal outgrowth that acts via Rab11 in a Cdk5-dependent manner.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Tetsuya TakanoShin-Ichi Hisanaga

Abstract

Axonal outgrowth is a coordinated process of cytoskeletal dynamics and membrane trafficking; however, little is known about proteins responsible for regulating the membrane supply. LMTK1 (lemur kinase 1)/AATYK1 (apoptosis-associated tyrosine kinase 1) is a serine/threonine kinase that is highly expressed in neurons. We recently reported that LMTK1 plays a role in recycling endosomal trafficking in CHO-K1 cells. Here we explore the role of LMTK1 in axonal outgrowth and its regulation by Cdk5 using mouse brain cortical neurons. LMTK1 was expressed and was phosphorylated at Ser34, the Cdk5 phosphorylation site, at the time of axonal outgrowth in culture and colocalized with Rab11A, the small GTPase that regulates recycling endosome traffic, at the perinuclear region and in the axon. Overexpression of the unphosphorylated mutant LMTK1-S34A dramatically promoted axonal outgrowth in cultured neurons. Enhanced axonal outgrowth was diminished by the inactivation of Rab11A, placing LMTK1 upstream of Rab11A. Unexpectedly, the downregulation of LMTK1 by knockdown or gene targeting also significantly enhanced axonal elongation. Rab11A-positive vesicles were transported anterogradely more quickly in the axons of LMTK1-deficient neurons than...Continue Reading

Citations

Mar 29, 2014·Molecular Biology of the Cell·Tetsuya TakanoShin-Ichi Hisanaga
Nov 7, 2015·Trends in Cell Biology·Petra van BergeijkLukas C Kapitein
May 23, 2014·Development, Growth & Differentiation·Takeshi Kawauchi
Mar 20, 2013·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Takahiro FuchigamiShin-ichi Hisanaga
Feb 13, 2014·Journal of Neurochemistry·David Villarroel-CamposChristian Gonzalez-Billault
May 15, 2015·Development, Growth & Differentiation·Takuro Tojima, Hiroyuki Kamiguchi
Aug 1, 2015·Molecular Neurobiology·Shu-Lei LiuJin-Tai Yu
Jul 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Kexin LiEviatar Nevo
Sep 8, 2016·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Govinda SharmaShin-Ichi Hisanaga
Apr 29, 2016·Cytoskeleton·David Villarroel-CamposChristian Gonzalez-Billault
Sep 26, 2015·PloS One·Cristina Isabel AriasCecilia Conde
Feb 2, 2017·Small GTPases·Maria Lidia Mignogna, Patrizia D'Adamo
Aug 10, 2016·Developmental Neurobiology·Kelly BarfordBettina Winckler
May 12, 2017·RNA Biology·Aron KosArmaz Aschrafi
Mar 21, 2018·Neuroscience Bulletin·Chunxia JiangXiaofeng Zhao
Apr 25, 2020·The International Journal of Neuroscience·Jiajia ZhangZhenchang Zhang
Sep 24, 2020·Scientific Reports·Miyuki TakahashiShin-Ichi Hisanaga
Apr 14, 2016·Biochemical Society Transactions·Camilla RaiborgHarald Stenmark
Sep 11, 2020·Cell Death and Differentiation·Dongdong ZhaoYun-Wu Zhang
Jul 28, 2020·Frontiers in Molecular Neuroscience·Shin-Ichi HisanagaMineko Tomomura
Nov 2, 2017·Developmental Neurobiology·Santiago QuirogaAlfredo Cáceres
Apr 27, 2018·Cellular and Molecular Life Sciences : CMLS·Sophie M HapakSourav Ghosh
Jun 28, 2017·Nature Communications·Tetsuya TakanoKozo Kaibuchi
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Victoria Rozés-SalvadorCecilia Conde
Mar 7, 2021·International Journal of Molecular Sciences·Veselina PetrovaRichard Eva
Jun 18, 2015·Development·Tetsuya TakanoKozo Kaibuchi
Dec 21, 2014·Biology Open·Tomoaki SobajimaAkihiro Harada
Jan 1, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Franz WendlerGeorgios Giamas
May 12, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Sebastian O SiriCecilia Conde
Sep 16, 2021·Journal of Biochemistry·Keisuke KomakiShin-Ichi Hisanaga

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