{"doi":"10.1093/jleuko/qiae197","title":"Glia maturation factor-γ regulates amyloid-β42 phagocytosis through scavenger receptor class A type I in murine macrophages","abstract":"Dysfunctional phagocytic clearance of β-amyloid (Aβ) in microglia and peripheral macrophages/monocytes has been implicated in Alzheimer's disease, but the mechanisms underlying this dysfunction are not yet well understood. In this study, we examined the role of glia maturation factor-γ (GMFG), an actin-disassembly protein, i.e. highly expressed in immune cells, in macrophage Aβ phagocytosis and in regulating type I class A scavenger receptor, a cell-surface receptor that has previously been implicated in Aβ clearance. GMFG knockdown-increased phagocytosis of Aβ42 in bone marrow-derived macrophages and RAW264.7 murine macrophages, while GMFG overexpression reduced Aβ42 uptake in these cells. Blocking with anti-type I class A scavenger receptor antibodies inhibited Aβ42 uptake in GMFG-knockdown cells, establishing a role for type I class A scavenger receptor in Aβ42 phagocytosis. GMFG knockdown-increased type I class A scavenger receptor protein expression under both basal conditions and in response to Aβ42 treatment via both the transcriptional and posttranscriptional levels in RAW264.7 macrophages. GMFG knockdown modulated Aβ42-induced K48-linked and K63-polyubiquitination of type I class A scavenger receptor, the phosphorylation of type I class A scavenger receptor and c-Jun N-Terminal kinase (JNK), suggesting that GMFG plays a role for intracellular signaling in the type I class A scavenger receptor--mediated uptake of Aβ. Further, GMFG-knockdown cells displayed increased levels of the transcriptional factor MafB, and silencing of MafB in these cells reduced their type I class A scavenger receptor expression. Finally, GMFG was found to interact with the nuclear pore complex component RanBP2, and silencing of RanBP2 in GMFG-knockdown cells reduced their type I class A scavenger receptor expression. Collectively, these data support the role of GMFG as a novel regulator of type I class A scavenger receptor in macrophage Aβ phagocytosis and may provide insight into therapeutic approaches to potentially slow or prevent the progression of Alzheimer's disease.","journal":"Journal of Leukocyte Biology","year":2024,"id":502990,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":386790,"name":"Jianqiong Zhu","orcid":null,"position":1,"is_corresponding":false},{"id":386791,"name":"Kyung Chin","orcid":null,"position":2,"is_corresponding":false},{"id":385547,"name":"Griffin P. Rodgers","orcid":"0000-0002-4710-0012","position":3,"is_corresponding":false},{"id":911945,"name":"Wulin Aerbajinai","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T02:10:27.781502Z","pmid":"39243388","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}