Bibliographic Details
| 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 |
| Authors: |
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, Reto |
| Source: |
Molecular Biology of the Cell; 20240101, Issue: Preprints |
| Abstract: |
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–Hook–FHIP (FHF) complex. By contrast, the C. elegansHook homolog 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 homologs of FTS (UBC-19) and FHIP (FHIP-1) that constitute the C. elegansFHF complex, validate the predicted FHIP-1–RAB-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. elegansHook adaptor evolved to recruit dynein to two distinct organelles, and that cargo specificity of ZYG-12 is regulated by alternative splicing. |
| Database: |
Supplemental Index |
