{
  "abstract": "Microglia rely on lysosomes to clear phagocytosed material and orchestrate immune responses, but the mechanisms governing glial lysosome diversity and function remain largely undefined. Using high-resolution, high-throughput 3D imaging of mouse brain tissue, we find that glial lysosomes are heterogeneous in size and protease content depending on subcellular location. CD68+ and LAMP1+ vesicles were more numerous in glial processes than cell bodies; process LAMP1+ vesicles carried less protease than cell-body vesicles, but CD68+ protease content did not differ between compartments, revealing at least two lysosomal subpopulations within processes. Loss of Adaptor Protein complex 4 (AP-4) selectively remodels this landscape: it increases CD68+ vesicle number and CD68 enrichment, particularly in processes, without changing protease content, and disrupts the normal cell-body-versus-process pattern in protease- and CD68-enrichment. AP-4 loss also lowers protease content in cell-body LAMP1+ vesicles, mirroring a neuronal phenotype. These results provide the first evidence of glial lysosome heterogeneity and implicate AP-4 in shaping microglial lysosome composition and inflammatory function.",
  "abstract_shown": true,
  "affiliations": [
    "University of Illinois at Chicago"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "E. Somodji"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Gowrishankar"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5kkx5xgen7mws.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.752408",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752408v1.full",
  "id": "5kkx5xgen7mws",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752408v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cell biology"
    ],
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7213537109",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752408v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5kkx5xgen7mws.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:04Z",
      "native_id": "10.64898/2026.09.17.752408",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.752408v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4",
  "title_text": "Compartment-Specific Lysosomal Heterogeneity in Microglia Is Regulated by Adaptor Protein Complex-4",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:04Z",
  "url": "https://research.draconitic.com/paper/5kkx5xgen7mws",
  "venue": "bioRxiv",
  "versions": []
}