{
  "abstract": "Spatial control of G-protein-coupled receptor (GPCR) signaling, which is used by cells to translate complex information into distinct downstream responses, is achieved by using plasma membrane (PM) and endocytic-derived signaling pathways. The roles of the endomembrane in regulating such pleiotropic signaling via multiple G-protein pathways remain unknown. Here, we investigated the effects of disease-causing mutations of the adaptor protein-2 σ subunit (AP2σ) on signaling by the class C GPCR calcium-sensing receptor (CaSR). These AP2σ mutations increase CaSR PM expression yet paradoxically reduce CaSR signaling. Hypercalcemia-associated AP2σ mutations reduced CaSR signaling via Gα q/11 and Gα i/o pathways. The mutations also delayed CaSR internalization due to prolonged residency time of CaSR in clathrin structures that impaired or abolished endosomal signaling, which was predominantly mediated by Gα q/11 . Thus, compartmental bias for CaSR-mediated Gα q/11 endomembrane signaling provides a mechanistic basis for multidimensional GPCR signaling.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "Caroline Gorvin"
    },
    {
      "name": "Angela Rogers"
    },
    {
      "name": "Benoit Hastoy"
    },
    {
      "name": "Andrei Tarasov"
    },
    {
      "name": "Morten Frost"
    },
    {
      "name": "Silvia Sposini"
    },
    {
      "name": "Asuka Inoue"
    },
    {
      "name": "Michael Whyte"
    },
    {
      "name": "Patrik Rorsman"
    },
    {
      "name": "Aylin Hanyaloglu"
    },
    {
      "name": "Gerda Breitwieser"
    },
    {
      "name": "Rajesh Thakker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bmxenft1j5jn1.bib",
  "cited_by": 86,
  "doi": "10.1016/j.celrep.2017.12.089",
  "fulltext_url": null,
  "id": "bmxenft1j5jn1",
  "issns": [
    "2211-1247",
    "2211-1247"
  ],
  "landing_url": "https://hal.science/hal-05767784v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1312|Receptor Mechanisms and Signaling"
    ]
  ],
  "openalex": "W2784844578",
  "pdf_url": "http://www.cell.com/article/S2211124717319265/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": "Elsevier Inc",
  "ris": "https://research.draconitic.com/paper/bmxenft1j5jn1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:42Z",
      "native_id": "hal-05767784",
      "source": "hal",
      "url": "https://hal.science/hal-05767784v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Receptor Mechanisms and Signaling",
      "subfield": "molecular-biology"
    }
  ],
  "title": "AP2σ Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity",
  "title_text": "AP2σ Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:42Z",
  "url": "https://research.draconitic.com/paper/bmxenft1j5jn1",
  "venue": "Cell Reports",
  "versions": []
}