Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity.
Open accessAbstract
Polarization of mammalian neurons with a specified axon requires precise regulation of microtubule and actin dynamics in the developing neurites. Here we show that mammalian partition defective 3 (mPar3), a key component of the Par polarity complex that regulates the polarization of many cell types including neurons, directly regulates microtubule stability and organization. The N-terminal portion of mPar3 exhibits strong microtubule binding, bundling, and stabilization activity, which can be suppressed by its C-terminal portion via an intramolecular interaction. Interestingly, the intermolecular oligomerization of mPar3 is able to relieve the intramolecular interaction and thereby promote microtubule bundling and stabilization. Furthermore, disruption of this microtubule regulatory activity of mPar3 impairs its function in axon specification. Together, these results demonstrate a role for mPar3 in directly regulating microtubule organization that is crucial for neuronal polarization.
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Par3 acts as a microtubule-binding protein that bundles and stabilizes microtubules to promote axon extension.
“Recently, it was shown that Par3 also acts as a microtubule-binding protein that bundles and stabilizes microtubules to promote axon extension (Chen et al., 2013).”
From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Chen et al., 2013
The Results section reports that mPar3 directly binds and bundles microtubules, and the Discussion says it stabilizes them in the emerging axon. The paper links this activity to axon specification and neuronal polarization, but does not establish that it promotes axon extension; the Results instead report impaired axonal outgrowth with mPar3 overexpression. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPar3's concentration-dependent oligomerization determines its ability to bind microtubules.
“Its concentration-dependent oligomerization determines its ability to bind microtubules.”
From Rassf5 and Ndr kinases act in a novel pathway regulating neuronal polarity through Par3 phosphorylation (2014) · cites this paper as Chen et al., 2013
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- Authors
- Chen, S., Chen, J., Shi, H., Wei, M., Castaneda-Castellanos, D. R., Bultje, R. S., Pei, X., Kriegstein, A. R., Zhang, M., & Shi, S.-H.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Hong Kong University of Science and Technology (HK)
- Rockefeller University (US)
- University of California, San Francisco (US)
- Corresponding author
- Chen, She
- Shi, Song-Hai
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 24
- Issue
- 1
- Pages
- 26-40
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3549028
- OpenAlex
- W2080846265
- Cited by
- 82
- References
- 67
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 6 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 10 · 2016: 3 · 2015: 6 · 2014: 9 · 2013: 9 · 2012: 1
- FWCI
- 3.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- Funders
- National Institutes of Health (PO1NS048120, R01DA024681)
- March of Dimes Foundation
- McKnight Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- neuronal polarity, axon specification, microtubule stabilization, microtubule bundling, intramolecular interactions, oligomerization, microtubule dynamics, actin dynamics, neurite development
- MeSH terms
- Amino Acid Sequence, Animals, Axons, Cells, Cultured, Cytoskeleton, Hippocampus, Microtubules, Molecular Sequence Data, Neurons, Signal Transduction, Cell Adhesion Molecules, Cell Polarity, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Cell Cycle Proteins, COS Cells, Fluorescence Resonance Energy Transfer, RNA, Small Interfering, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Mice, Neurogenesis
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