{"doi":"10.7554/elife.84798","title":"Hsp47 promotes biogenesis of multi-subunit neuroreceptors in the endoplasmic reticulum","abstract":"Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurological and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is poorly understood. Previous proteomics studies identified Hsp47 (Gene: SERPINH1 ), a heat shock protein in the endoplasmic reticulum lumen, as the most enriched interacting chaperone for gamma-aminobutyric acid type A (GABA A ) receptors. Here, we show that Hsp47 enhances the functional surface expression of GABA A receptors in rat neurons and human HEK293T cells. Furthermore, molecular mechanism study demonstrates that Hsp47 acts after BiP (Gene: HSPA5 ) and preferentially binds the folded conformation of GABA A receptors without inducing the unfolded protein response in HEK293T cells. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABA A receptors. Overexpressing Hsp47 is sufficient to correct the surface expression and function of epilepsy-associated GABA A receptor variants in HEK293T cells. Hsp47 also promotes the surface trafficking of other Cys-loop receptors, including nicotinic acetylcholine receptors and serotonin type 3 receptors in HEK293T cells. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 plays a critical and general role in the maturation of multi-subunit Cys-loop neuroreceptors.","journal":"eLife","year":2024,"id":462874,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"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":482134,"name":"Xiao-Jing Di","orcid":null,"position":1,"is_corresponding":false},{"id":618401,"name":"Peipei Zhang","orcid":"0000-0003-1742-1680","position":2,"is_corresponding":false},{"id":1292713,"name":"Xi Chen","orcid":"0000-0002-5748-470X","position":3,"is_corresponding":false},{"id":1266342,"name":"Marnie P Williams","orcid":null,"position":4,"is_corresponding":false},{"id":482136,"name":"Dong‐Yun Han","orcid":null,"position":5,"is_corresponding":false},{"id":993615,"name":"Raad Nashmi","orcid":"0000-0001-6596-2620","position":6,"is_corresponding":false},{"id":304716,"name":"Brandon J. Henderson","orcid":"0000-0003-0381-028X","position":7,"is_corresponding":false},{"id":473820,"name":"Fraser J. Moss","orcid":"0000-0002-8519-6991","position":8,"is_corresponding":false},{"id":317,"name":"Ting-Wei Mu","orcid":"0000-0002-6419-9296","position":9,"is_corresponding":false},{"id":481312,"name":"Yajuan Wang","orcid":"0000-0002-3284-9012","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T02:04:24.680035Z","pmid":"38963323","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":[]}