title: LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.
abstract: Neurons extend two types of neurites-axons and dendrites-that differ in structure and function. Although it is well understood that the cytoskeleton plays a pivotal role in neurite differentiation and extension, the mechanisms by which membrane components are supplied to growing axons or dendrites is largely unknown. We previously reported that the membrane supply to axons is regulated by lemur kinase 1 (LMTK1) through Rab11A-positive endosomes. Here we investigate the role of LMTK1 in dendrite formation. Down-regulation of LMTK1 increases dendrite growth and branching of cerebral cortical neurons in vitro and in vivo. LMTK1 knockout significantly enhances the prevalence, velocity, and run length of anterograde movement of Rab11A-positive endosomes to levels similar to those expressing constitutively active Rab11A-Q70L. Rab11A-positive endosome dynamics also increases in the cell body and growth cone of LMTK1-deficient neurons. Moreover, a nonphosphorylatable LMTK1 mutant (Ser34Ala, a Cdk5 phosphorylation site) dramatically promotes dendrite growth. Thus LMTK1 negatively controls dendritic formation by regulating Rab11A-positive endosomal trafficking in a Cdk5-dependent manner, indicating the Cdk5-LMTK1-Rab11A pathway as a regulatory mechanism of dendrite development as well as axon outgrowth.
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan takano-tetsuya@ed.tmu.ac.jp hisanaga-shinichi@tmu.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takano
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Urushibara
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Yoshioka
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
authors.affiliation: Meikai Pharmaco-Medical Laboratory, Meikai University School of Dentistry, Sakado 350-0283, Japan.
authors.forename: Mineko
authors.initials: M
authors.lastname: Tomomura
authors.affiliation: Department of Biological Sciences, Tokyo Metropolitan University, Tokyo 192-0397, Japan takano-tetsuya@ed.tmu.ac.jp hisanaga-shinichi@tmu.ac.jp.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hisanaga
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000378:metabolism*; D001369:Axons / Q000378:metabolism; D066146:Cell Body / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D015536:Down-Regulation; D011992:Endosomes / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism; D008813:Mice, Inbred ICR; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000378:metabolism*; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000099193:rab11 GTP-Binding Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D050505:Mutant Proteins; D010768:Phosphoserine; D011505:Protein-Tyrosine Kinases; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C485554:Aatk protein, mouse