ArticleProceedings of the National Academy of Sciences of the United States of America2006
Microtubule affinity-regulating kinase 2 functions downstream of the PAR-3/PAR-6/atypical PKC complex in regulating hippocampal neuronal polarity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 154 citations in OpenAlex.
- Meta-analysis of genome-wide association studies identifies ancestry-specific associations underlying circulating total tau levels.Communications biology · 2022Pooled it
- NAT10 promotes prostate cancer progression by acetylating mRNA of MARK2 and activating mTOR/HIF-1α/C-Myc pathway to enhance glycolytic reprogramming.Cancer gene therapy · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Case Report: Epileptic phenotype in a patient with aFrontiers in pediatrics · 2026Article
- Constructive Neuroengineering of Axon Polarization Control Using Modifiable Agarose Gel Platforms for Neuronal Circuit Construction.Gels (Basel, Switzerland) · 2025Article
- MARK2 variants cause autism spectrum disorder via the downregulation of WNT/β-catenin signaling pathway.American journal of human genetics · 2024Article
- Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Atypical Protein Kinase C Promotes its own Asymmetric Localisation by Phosphorylating Cdc42 in thebioRxiv : the preprint server for biology · 2024Article
- MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Role of MARK2 in the nervous system and cancer.Cancer gene therapy · 2024Review
- Single-molecule imaging reveals Tau trapping at nanometer-sized dynamic hot spots near the plasma membrane that persists after microtubule perturbation and cholesterol depletion.The EMBO journal · 2022Article
- Liver Kinase B1 Functions as a Regulator for Neural Development and a Therapeutic Target for Neural Repair.Cells · 2022Review
- MARK2 regulates directed cell migration through modulation of myosin II contractility and focal adhesion organization.Current biology : CB · 2022Article
- 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
- A novel non‑selective atypical PKC agonist could protect neuronal cell line from Aβ‑oligomer induced toxicity by suppressing Aβ generation.Molecular medicine reports · 2022Article
- Perspectives on Mechanisms Supporting Neuronal Polarity From Small Animals to Humans.Frontiers in cell and developmental biology · 2022Review
- CAMSAP1 breaks the homeostatic microtubule network to instruct neuronal polarity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- PTPRA Phosphatase Regulates GDNF-Dependent RET Signaling and Inhibits the RET Mutant MEN2A Oncogenic Potential.iScience · 2020Article
- aPKC in neuronal differentiation, maturation and function.Neuronal signaling · 2019Review
- Memantine Improves Cognitive Function and Alters Hippocampal and Cortical Proteome in Triple Transgenic Mouse Model of Alzheimer's Disease.Experimental neurobiology · 2019Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PAR-3/PAR-6/atypical PKC (aPKC) complex is required for axon-dendrite specification of hippocampal neurons. However, the downstream effectors of this complex are not well defined. In this article, we report a role for microtubule affinity-regulating kinase (MARK)/PAR-1 in axon-dendrite specification. Knocking down MARK2 expression with small interfering RNAs induced formation of multiple axon-like neurites and promoted axon outgrowth. Ectopic expression of MARK2 caused phosphorylation of tau (S262) and led to loss of axons, and this phenotype was rescued by expression of PAR-3, PAR-6, and aPKC. In contrast, the polarity defects caused by an MARK2 mutant (T595A), which is not responsive to aPKC, were not rescued by the PAR-3/PAR-6/aPKC complex. Moreover, polarity was abrogated in neurons overexpressing a mutant of MARK2 with a deleted kinase domain but an intact aPKC-binding domain. Finally, suppression of MARK2 rescued the polarity defects induced by a dominant-negative aPKC mutant. These results suggest that MARK2 is involved in neuronal polarization and functions downstream of the PAR-3/PAR-6/aPKC complex. We propose that aPKC in complex with PAR-3/PAR-6 negatively regulates MARK(s), which in turn causes dephosphorylation of microtubule-associated proteins, such as tau, leading to the assembly of microtubules and elongation of axons.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.