LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes

Tetsuya Takano, Tomoki Urushibara, Nozomu Yoshioka, Taro Saito, Mitsunori Fukuda, Mineko Tomomura, Shin Ichi Hisanaga

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1755-1768
    Number of pages14
    JournalMolecular biology of the cell
    Volume25
    Issue number11
    DOIs
    Publication statusPublished - 2014 Jun 1

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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