Browsing by Author "Moreira, Matilde"
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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 domainPublication . Carvalho, Cátia; Moreira, Matilde; Barbosa, Daniel J.; Chan, Fung-Yi; Koehnen, Carlota Boal; Teixeira, Vanessa; Rocha, Helder; Green, Mattie; Carvalho, Ana Xavier; Cheerambathur, Dhanya K.; Gassmann, RetoThe 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.