Intralumenal docking of connexin 36 channels in the ER isolates mistrafficked protein
Autor(en): | Tetenborg, Stephan Liss, Viktoria Breitsprecher, Leonhard Timonina, Ksenia Kotova, Anna Acevedo Harnecker, Alejandra Jesús Yuan, Chunxu Shihabeddin, Eyad Ariakia, Fatemeh Qin, Guoting Chengzhi, Cai Dedek, Karin Zoidl, Georg Hensel, Michael O'Brien, John |
Stichwörter: | Article; binding site; connexin; connexin 36; controlled study; correlated light, and electron microscopy; cysteine; Cytology; cytoplasm; embryo; endoplasmic reticulum; endoplasmic reticulum membrane; Gap-junctions; HEK293T cell line; hemichannels; human; human cell; Intracellular domain; Intraluminal; membrane vesicle; molecular docking; Multi-lamellar vesicles; multilamellar vesicles; mutant; PDZ binding motif; phenotype; premature docking; protein aggregation; protein transport; site directed mutagenesis | Erscheinungsdatum: | 2023 | Herausgeber: | American Society for Biochemistry and Molecular Biology Inc. | Journal: | Journal of Biological Chemistry | Volumen: | 299 | Ausgabe: | 11 | Zusammenfassung: | 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. © 2023 The Authors |
Beschreibung: | Cited by: 0; All Open Access, Gold Open Access |
ISSN: | 0021-9258 | DOI: | 10.1016/j.jbc.2023.105282 | Externe URL: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85174922462&doi=10.1016%2fj.jbc.2023.105282&partnerID=40&md5=4a952f58f4ac27e2d44f82db5b83f7d2 |
Zur Langanzeige
Seitenaufrufe
2
Letzte Woche
0
0
Letzter Monat
1
1
geprüft am 21.05.2024