{
  "abstract": "Cyclin-dependent kinase like 5 (CDKL5) is a serine-threonine kinase enriched in the mammalian brain whose loss of function causes a severe developmental and epileptic encephalopathy named CDKL5 Deficiency Disorder. We previously showed that CDKL5 phosphorylates the microtubule-associated protein MAP1S, but how this regulates microtubule-dependent functions is not well understood. To address this question, we generated MAP1S phosphomutant mice in which the CDKL5 phosphorylation sites S786 and S812 were mutated to alanine (MAP1S S786/812A; MAP1S SA). Using a microtubule cosedimentation assay, we found that dynein binding to microtubules was reduced in MAP1S SA and CDKL5 knockout (KO) brain lysates, and time-lapse imaging showed impaired dynein motility in dendrites from both genotypes. MAP1S SA mice also exhibited reduced AMPA receptor transport, dendritic spine density, and excitatory synapses, accompanied by anxiety-like behavior and motor, social, and memory deficits relevant to CDD. Mechanistically, MAP1S SA and CDKL5 KO neurons showed increased microtubule stability and reduced tubulin tyrosination, consistent with excessive MAP1S-mediated stabilization. Restoring tubulin tyrosination by expressing tubulin-tyrosine ligase rescued dynein transport defects. Together, these findings identify MAP1S phosphorylation as a critical regulator of microtubule dynamics and dynein-dependent transport.",
  "abstract_shown": true,
  "affiliations": [
    "Kinases and Brain Development Lab, The Francis Crick Institute, London, United Kingdom."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "André T. Lopes",
      "orcid": "0000-0001-9920-5556"
    },
    {
      "affs": [
        0
      ],
      "name": "Ondine Janiv"
    },
    {
      "affs": [
        0
      ],
      "name": "Suzanne Claxton"
    },
    {
      "affs": [
        0
      ],
      "name": "Sila K. Ultanir"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cbah9ysh6kjpj.bib",
  "cited_by": 0,
  "doi": "10.1172/jci188241",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722393/",
  "id": "cbah9ysh6kjpj",
  "issns": [
    "0021-9738",
    "1558-8238"
  ],
  "landing_url": "https://doi.org/10.1172/jci188241",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1307|Microtubule and mitosis dynamics"
    ]
  ],
  "openalex": "W7214175564",
  "pdf_url": "http://www.jci.org/articles/view/188241/files/pdf",
  "pmcid": "PMC13722393",
  "pmid": "42784707",
  "published": "2026-09-15",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/cbah9ysh6kjpj.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:22:54Z",
      "native_id": "PMC13722393",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci188241"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Microtubule and mitosis dynamics",
      "subfield": "cell-biology"
    }
  ],
  "title": "Microtubule-associated protein 1S phosphorylation regulates dynein-driven transport and synaptogenesis in neurons",
  "title_text": "Microtubule-associated protein 1S phosphorylation regulates dynein-driven transport and synaptogenesis in neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:54Z",
  "url": "https://research.draconitic.com/paper/cbah9ysh6kjpj",
  "venue": "The Journal of Clinical Investigation",
  "versions": []
}