CAMSAP3 maintains neuronal polarity through regulation of microtubule stability.

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  • Additional Information
    • Source:
      Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, DC : National Academy of Sciences
    • Subject Terms:
      Cell Polarity*; Microtubule-Associated Proteins/*physiology ; Microtubules/*metabolism ; Neurons/*metabolism; Acetylation ; Animals ; Hippocampus/cytology ; Mice ; Mice, Knockout ; Tubulin/metabolism
    • Abstract:
      The molecular mechanisms that guide each neuron to become polarized, forming a single axon and multiple dendrites, remain unknown. Here we show that CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a protein that regulates the minus-end dynamics of microtubules, plays a key role in maintaining neuronal polarity. In mouse hippocampal neurons, CAMSAP3 was enriched in axons. Although axonal microtubules were generally acetylated, CAMSAP3 was preferentially localized along a less-acetylated fraction of the microtubules. CAMSAP3-mutated neurons often exhibited supernumerary axons, along with an increased number of neurites having nocodazole-resistant/acetylated microtubules compared with wild-type neurons. Analysis using cell lines showed that CAMSAP3 depletion promoted tubulin acetylation, and conversely, mild overexpression of CAMSAP3 inhibited it, suggesting that CAMSAP3 works to retain nonacetylated microtubules. In contrast, CAMSAP2, a protein related to CAMSAP3, was detected along all neurites, and its loss did not affect neuronal polarity, nor did it cause increased tubulin acetylation. Depletion of α-tubulin acetyltransferase-1 (αTAT1), the key enzyme for tubulin acetylation, abolished CAMSAP3 loss-dependent multiple-axon formation. These observations suggest that CAMSAP3 sustains a nonacetylated pool of microtubules in axons, interfering with the action of αTAT1, and this process is important to maintain neuronal polarity.
      Competing Interests: The authors declare no conflict of interest.
      (Copyright © 2018 the Author(s). Published by PNAS.)
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    • Grant Information:
      United Kingdom Wellcome Trust
    • Contributed Indexing:
      Keywords: CAMSAP; axon; microtubule; neuronal polarity; αTAT1
    • Accession Number:
      0 (Camsap3 protein, mouse)
      0 (Microtubule-Associated Proteins)
      0 (Tubulin)
    • Publication Date:
      Date Created: 20180908 Date Completed: 20181022 Latest Revision: 20181114
    • Publication Date:
      20221213
    • Accession Number:
      PMC6166842
    • Accession Number:
      10.1073/pnas.1803875115
    • Accession Number:
      30190432