{"doi":"10.1016/j.jbc.2023.105282","title":"Intralumenal docking of connexin 36 channels in the ER isolates mistrafficked protein","abstract":"The intracellular domains of connexins are essential for the assembly of gap junctions. For connexin 36 (Cx36), the major neuronal connexin, it has been shown that a dysfunctional PDZ-binding motif interferes with electrical synapse formation. However, it is still unknown how this motif coordinates the transport of Cx36. In the present study, we characterize a phenotype of Cx36 mutants that lack a functional PDZ-binding motif using HEK293T cells as an expression system. We provide evidence that an intact PDZ-binding motif is critical for proper endoplasmic reticulum (ER) export of Cx36. Removing the PDZ-binding motif of Cx36 results in ER retention and the formation of multimembrane vesicles containing gap junction-like connexin aggregates. Using a combination of site-directed mutagenesis and electron micrographs, we reveal that these vesicles consist of Cx36 channels that docked prematurely in the ER. Our data suggest a model in which ER-retained Cx36 channels reshape the ER membrane into concentric whorls that are released into the cytoplasm.","journal":"Journal of Biological Chemistry","year":2023,"id":343314,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9545,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":996222,"name":"Viktoria Liss","orcid":"0000-0002-1304-2512","position":1,"is_corresponding":false},{"id":996223,"name":"Leonhard Breitsprecher","orcid":"0000-0001-9880-5939","position":2,"is_corresponding":false},{"id":996224,"name":"Ksenia Timonina","orcid":"0000-0002-6006-8467","position":3,"is_corresponding":false},{"id":996697,"name":"Anna Kotova","orcid":null,"position":4,"is_corresponding":false},{"id":996225,"name":"Alejandra Jesús Acevedo Harnecker","orcid":"0000-0001-5579-2437","position":5,"is_corresponding":false},{"id":996698,"name":"Chunxu Yuan","orcid":null,"position":6,"is_corresponding":false},{"id":385273,"name":"Eyad Shihabeddin","orcid":"0000-0002-3140-1523","position":7,"is_corresponding":false},{"id":1080828,"name":"Fatemeh Ariakia","orcid":"0000-0003-3016-2978","position":8,"is_corresponding":false},{"id":940378,"name":"Guoting Qin","orcid":"0000-0001-8916-6311","position":9,"is_corresponding":false},{"id":1081349,"name":"Cai Chengzhi","orcid":null,"position":10,"is_corresponding":false},{"id":371178,"name":"Karin Dedek","orcid":"0000-0003-1490-0141","position":11,"is_corresponding":false},{"id":772341,"name":"Georg Zoidl","orcid":"0000-0003-1163-3260","position":12,"is_corresponding":false},{"id":846716,"name":"Michael Hensel","orcid":"0000-0001-6604-6253","position":13,"is_corresponding":false},{"id":269817,"name":"John O’Brien","orcid":"0000-0002-0270-3442","position":14,"is_corresponding":false},{"id":371173,"name":"Stephan Tetenborg","orcid":"0000-0002-9025-0446","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:11:21.758449Z","pmid":"37742923","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":[]}