{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:49:24Z","timestamp":1771051764690,"version":"3.50.1"},"reference-count":40,"publisher":"American Society for Cell Biology (ASCB)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2025,2,1]]},"abstract":"<jats:p> The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS\u2013Hook\u2013FHIP (FHF) complex. By contrast, the Caenorhabditis elegans Hook homologue ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex. Here, we demonstrate that ZYG-12 recruits dynein to EE in epithelia. We identify and functionally characterize the homologues of FTS (UBC-19) and FHIP (FHIP-1) that constitute the C. elegans FHF complex, validate the predicted FHIP-1\u2013RAB-5 binding interface in vivo, and show that ZYG-12 forms FHF via a conserved segment that precedes, and is distinct from, its C-terminal NE targeting domain. Finally, we show that 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 distinct organelles, and that cargo specificity of ZYG-12 is regulated by alternative splicing. <\/jats:p>","DOI":"10.1091\/mbc.e24-08-0364","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T16:18:56Z","timestamp":1735057136000},"source":"Crossref","is-referenced-by-count":5,"title":["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"],"prefix":"10.1091","volume":"36","author":[{"given":"C\u00e1tia","family":"Carvalho","sequence":"first","affiliation":[{"name":"i3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"IBMC \u2013 Instituto de Biologia Molecular e Celular, 4200-135 Porto, Portugal"},{"name":"ICBAS \u2013 Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 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