ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
ERK2-mediated phosphorylation of Par3 regulates neuronal polarization.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- Advances in Understanding the Molecular Mechanisms of Neuronal Polarity.Molecular neurobiology · 2023Review
- Liver Kinase B1 Functions as a Regulator for Neural Development and a Therapeutic Target for Neural Repair.Cells · 2022Review
- The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Review
- Integrative proteogenomic characterization of hepatocellular carcinoma across etiologies and stages.Nature communications · 2022Review
- The polarity protein PARD3 and cancer.Oncogene · 2021Review
- Tuba Activates Cdc42 during Neuronal Polarization Downstream of the Small GTPase Rab8a.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- RAS-mediated suppression of PAR3 and its effects on SCC initiation and tissue architecture occur independently of hyperplasia.Journal of cell science · 2020Article
- Tyrosine-Based Signals Regulate the Assembly of Daple⋅PARD3 Complex at Cell-Cell Junctions.iScience · 2020Article
- Linking Cell Polarity to Cortical Development and Malformations.Frontiers in cellular neuroscience · 2019Review
- Neuronal Polarity: Positive and Negative Feedback Signals.Frontiers in cell and developmental biology · 2019Article
- PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization.Cellular and molecular life sciences : CMLS · 2018Review
- Neuronal Polarity in the Embryonic Mammalian Cerebral Cortex.Frontiers in cellular neuroscience · 2017Review
- Decoding the molecular mechanisms of neuronal migration using in utero electroporation.Medical molecular morphology · 2016Review
- Radial Glial Cell-Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.Schizophrenia bulletin · 2015Article
- Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.Nature neuroscience · 2015Article
- Neuronal polarization in the developing cerebral cortex.Frontiers in neuroscience · 2015Review
- Rassf5 and Ndr kinases regulate neuronal polarity through Par3 phosphorylation in a novel pathway.Journal of cell science · 2014Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Axon formation is one of the most important events in neuronal polarization and is regulated by signaling molecules involved in cytoskeletal rearrangement and protein transport. We previously found that Partition-defective 3 (Par3) is associated with KIF3A (kinesin-2) and is transported into the nascent axon in a KIF3A-dependent fashion. Par3 interacts with the Rac-specific guanine nucleotide-exchange factors (GEFs) Tiam1/2, which activate Rac1, and participates in axon formation in cultured hippocampal neurons. However, the regulatory mechanism of the Par3-KIF3A interaction is poorly understood, and the role of Par3 in neuronal polarization in vivo remains elusive. Here, we found that extracellular signal-regulated kinase 2 (ERK2) directly interacts with Par3, that ERK2 phosphorylates Par3 at Ser-1116, and that the phosphorylated Par3 accumulates at the axonal tips in a manner dependent upon ERK2 activity. The phosphorylation of Par3 by ERK2 inhibited the interaction of Par3 with KIF3A but not with the other Par3 partners, including Par6 and aPKC. The phosphomimic mutant of Par3 (Par3-S1116D) showed less binding activity with the KIF3s and slower transport in the axons. The knockdown of Par3 by RNA interference impaired neuronal polarization, which was rescued with RNAi-resistant Par3, but not with the phosphomimic Par3 mutant, in cultured rat hippocampal neurons and mouse cortical projection neurons in vivo. These results suggest that ERK2 phosphorylates Par3 and inhibits its binding with KIF3A, thereby controlling Par3 transport and neuronal polarity.
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