ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
LMTK1/AATYK1 is a novel regulator of axonal outgrowth that acts via Rab11 in a Cdk5-dependent manner.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Traffic Jams in the Brain: How Kinesin Dysfunction Shapes Neurodevelopmental Disorders.Current issues in molecular biology · 2026Review
- The Recycling Endosomal (NaActa physiologica (Oxford, England) · 2026Article
- Restoration neurite growth by removing the blockage of endosome trafficking in Alzheimer-like mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Distribution analysis of RAB11A and RAB11B, small GTP-binding proteins, in mice.Molecular biology reports · 2025Article
- CDK5 Deficiency Does not Impair Neuronal Differentiation of Human Induced Pluripotent Stem Cells but Affects Neurite Outgrowth.Molecular neurobiology · 2025Article
- The lemur tail kinase family in neuronal function and disfunction in neurodegenerative diseases.Cellular and molecular life sciences : CMLS · 2024Review
- A Novel Constitutively ActiveHuman mutation · 2023Article
- Ubiquitin ligase activity inhibits Cdk5 to control axon termination.PLoS genetics · 2022Article
- Axonal Organelles as Molecular Platforms for Axon Growth and Regeneration after Injury.International journal of molecular sciences · 2021Review
- RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation.Cell death and differentiation · 2021Article
- Hyperactive and impulsive behaviors of LMTK1 knockout mice.Scientific reports · 2020Article
- Epigenetic silencing of AATK in acinar to ductal metaplasia in murine model of pancreatic cancer.Clinical epigenetics · 2020Article
- LMTK1, a Novel Modulator of Endosomal Trafficking in Neurons.Frontiers in molecular neuroscience · 2020Article
- The Recycling Endosome in Nerve Cell Development: One Rab to Rule Them All?Frontiers in cell and developmental biology · 2020Review
- Cyclin-Dependent Kinase-Like 5 (CDKL5): Possible Cellular Signalling Targets and Involvement in CDKL5 Deficiency Disorder.Neural plasticity · 2020Review
- The LMTK1-TBC1D9B-Rab11A Cascade Regulates Dendritic Spine Formation via Endosome Trafficking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization.Cellular and molecular life sciences : CMLS · 2018Review
- AATYK is a Novel Regulator of Oligodendrocyte Differentiation and Myelination.Neuroscience bulletin · 2018Article
- Critical importance of RAB proteins for synaptic function.Small GTPases · 2018Review
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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 in those of wild-type neurons. The enhanced axonal outgrowth was reversed by LMTK1-WT or the LMTK1-S34D mutant, which mimics the phosphorylated state, but not by LMTK1-S34A. Thus, LMTK1 can negatively control axonal outgrowth by regulating Rab11A activity in a Cdk5-dependent manner, and Cdk5-LMTK1-Rab11 is a novel signaling pathway involved in axonal outgrowth.
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