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ZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain

dc.contributor.authorCarvalho, Cátia
dc.contributor.authorMoreira, Matilde
dc.contributor.authorBarbosa, Daniel J.
dc.contributor.authorChan, Fung-Yi
dc.contributor.authorKoehnen, Carlota Boal
dc.contributor.authorTeixeira, Vanessa
dc.contributor.authorRocha, Helder
dc.contributor.authorGreen, Mattie
dc.contributor.authorCarvalho, Ana Xavier
dc.contributor.authorCheerambathur, Dhanya K.
dc.contributor.authorGassmann, Reto
dc.date.accessioned2025-10-21T09:59:21Z
dc.date.available2025-10-21T09:59:21Z
dc.date.issued2025-02-01
dc.description.abstractThe microtubule motor cytoplasmic dynein-1 transports and positions variousorganelles, but the molecular basis of this functional diversity is not fully understood. Cargoadaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi andhuman cells by forming the FTS–Hook–FHIP (FHF) complex. By contrast, the Caenorhabdi-tis elegans Hook homologue ZYG-12 recruits dynein to the nuclear envelope (NE) in themeiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cy-toskeleton (LINC) complex. Here, we demonstrate that ZYG-12 recruits dynein to EE inepithelia. We identify and functionally characterize the homologues of FTS (UBC-19) andFHIP (FHIP-1) that constitute the C. elegans FHF complex, validate the predicted FHIP-1–RAB-5 binding interface in vivo, and show that ZYG-12 forms FHF via a conserved segmentthat precedes, and is distinct from, its C-terminal NE targeting domain. Finally, we showthat C-terminal ZYG-12 splice isoforms differ in their ability to target to the NE and EE.We conclude that the C. elegans Hook adaptor evolved to recruit dynein to two distinctorganelles, and that cargo specificity of ZYG-12 is regulated by alternative splicing.por
dc.identifier.citationCarvalho, C., Moreira, M., Barbosa, D. J., Chan, F.-Y., Koehnen, C. B., Teixeira, V., Rocha, H., Green, M., Carvalho, A. X., Cheerambathur, D. K., & Gassmann, R. (2025). ZYG-12/Hook’s dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain. Molecular Biology of the Cell, 36(2), ar19. https://doi.org/10.1091/mbc.E24-08-0364
dc.identifier.doi10.1091/mbc.E24-08-0364
dc.identifier.eissn1939-4586
dc.identifier.issn1059-1524
dc.identifier.urihttp://hdl.handle.net/10400.22/30650
dc.language.isoeng
dc.peerreviewedyes
dc.publisherASCB - The American Society for Cell Biology
dc.relationPTDC/BIA-CEL/1321/2021
dc.relation.hasversionhttps://www.molbiolcell.org/doi/10.1091/mbc.E24-08-0364
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDynein adaptor
dc.subjectCargo binding domain
dc.titleZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domainpor
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue2
oaire.citation.titleMolecular Biology of the Cell
oaire.citation.volume36
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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