{"doi":"10.1101/2022.10.24.513629","title":"Hsp47 Promotes Biogenesis of Multi-subunit Neuroreceptors in the Endoplasmic Reticulum","abstract":"ABSTRACT Protein homeostasis (proteostasis) deficiency is an important contributing factor to neurodegenerative, neurological, and metabolic diseases. However, how the proteostasis network orchestrates the folding and assembly of multi-subunit membrane proteins is not well 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 type A (GABA A ) receptors. Here, we show that Hsp47 enhances neuronal GABA A receptor functional surface expression, acting after Binding immunoglobulin Protein (BiP) to preferentially bind the folded conformation of GABA A receptors. Therefore, Hsp47 promotes the subunit-subunit interaction, the receptor assembly process, and the anterograde trafficking of GABA A receptors. These Hsp47 properties are also extended to other Cys-loop receptors, including nicotinic acetylcholine receptors. Therefore, in addition to its known function as a collagen chaperone, this work establishes that Hsp47 also plays a critical and general role in the maturation of multi-subunit neuroreceptors. Highlights Hsp47 positively regulates the functional surface expression of endogenous GABA A receptors. Hsp47 acts after BiP and preferentially binds the folded conformation of GABA A receptors. Hsp47 promotes the subunit-subunit assembly of GABA A receptors. Hsp47 plays a critical and general role in the maturation of multi-subunit neuroreceptors.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302083,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","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":482136,"name":"Dong‐Yun Han","orcid":null,"position":2,"is_corresponding":false},{"id":993615,"name":"Raad Nashmi","orcid":"0000-0001-6596-2620","position":3,"is_corresponding":false},{"id":304716,"name":"Brandon J. Henderson","orcid":"0000-0003-0381-028X","position":4,"is_corresponding":false},{"id":473820,"name":"Fraser J. Moss","orcid":"0000-0002-8519-6991","position":5,"is_corresponding":false},{"id":317,"name":"Ting-Wei Mu","orcid":"0000-0002-6419-9296","position":6,"is_corresponding":false},{"id":481312,"name":"Yajuan Wang","orcid":"0000-0002-3284-9012","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T00:32:06.309890Z","pmid":null,"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":[]}