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

First Author  Takano T Year  2014
Journal  Mol Biol Cell Volume  25
Issue  11 Pages  1755-68
PubMed ID  24672056 Mgi Jnum  J:310918
Mgi Id  MGI:6762620 Doi  10.1091/mbc.E14-01-0675
Citation  Takano T, et al. (2014) LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes. Mol Biol Cell 25(11):1755-68
abstractText  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.
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