{
  "abstract": "The K-Cl cotransporter KCC2 is essential for fast synaptic inhibition in the mature brain. It is encoded by a single gene and expressed as two isoforms: KCC2a and KCC2b, which differ in their N-terminal domains. While KCC2b is predominant, the function of the weakly expressed KCC2a isoform remains unclear. Here, we reveal that KCC2a is a potent, bidirectional regulator of KCC2b membrane stability and function in cortical neurons. In immature neurons, where WNK-SPAK kinase activity is high, KCC2a promotes SPAK-dependent phosphorylation of KCC2b at Thr1007, which likely contributes to hindering its membrane expression and function. Conversely, in mature neurons with low basal WNK-SPAK activity, KCC2a promotes KCC2b expression, clustering, and function. At this stage, although accounting for less than 5% of total KCC2 mRNA, KCC2a is enriched in dendrites and within KCC2 clusters, where it prevents clathrin-mediated KCC2b endocytosis, as well as polyubiquitination and proteasomal degradation. Thus, KCC2a acts as a developmental switch that first inhibits KCC2b during early development and then ensures its membrane stability to support effective synaptic inhibition in the adult brain.",
  "abstract_shown": true,
  "affiliations": [
    "Institut du Fer à Moulin, Inserm, Sorbonne Université",
    "Department of Anatomy, Faculty of Medicine, University of Helsinki"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carla Pagan"
    },
    {
      "affs": [
        0
      ],
      "name": "Pauline Weinzettl"
    },
    {
      "affs": [
        1
      ],
      "name": "Marika A Markkanen"
    },
    {
      "affs": [
        0
      ],
      "name": "Marion Russeau"
    },
    {
      "affs": [
        1
      ],
      "name": "Matti S Airaksinen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jean-Christophe Poncer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9s6crtj26a83p.bib",
  "cited_by": 0,
  "doi": "10.1038/s44319-026-00920-3",
  "fulltext_url": "https://doi.org/10.1038/s44319-026-00920-3",
  "id": "9s6crtj26a83p",
  "issns": [
    "1469-3178"
  ],
  "landing_url": "https://doi.org/10.1038/s44319-026-00920-3",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "1312|Ion Transport and Channel Regulation"
    ]
  ],
  "openalex": "W7208809415",
  "pdf_url": "https://link.springer.com/content/pdf/10.1038/s44319-026-00920-3.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-01",
  "publisher": "Springer Nature",
  "ris": "https://research.draconitic.com/paper/9s6crtj26a83p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:46:19Z",
      "native_id": "3235dd10e87e4d7eb4911ee392760557",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s44319-026-00920-3"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Ion Transport and Channel Regulation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Differential isoform-specific control of KCC2 function in developing and mature cortical neurons",
  "title_text": "Differential isoform-specific control of KCC2 function in developing and mature cortical neurons",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:19Z",
  "url": "https://research.draconitic.com/paper/9s6crtj26a83p",
  "venue": "EMBO Reports",
  "versions": []
}