HookA is a novel dynein–early endosome linker critical for cargo movement in vivo
نویسندگان
چکیده
Cytoplasmic dynein transports membranous cargoes along microtubules, but the mechanism of dynein-cargo interaction is unclear. From a genetic screen, we identified a homologue of human Hook proteins, HookA, as a factor required for dynein-mediated early endosome movement in the filamentous fungus Aspergillus nidulans. HookA contains a putative N-terminal microtubule-binding domain followed by coiled-coil domains and a C-terminal cargo-binding domain, an organization reminiscent of cytoplasmic linker proteins. HookA-early endosome interaction occurs independently of dynein-early endosome interaction and requires the C-terminal domain. Importantly, HookA interacts with dynein and dynactin independently of HookA-early endosome interaction but dependent on the N-terminal part of HookA. Both dynein and the p25 subunit of dynactin are required for the interaction between HookA and dynein-dynactin, and loss of HookA significantly weakens dynein-early endosome interaction, causing a virtually complete absence of early endosome movement. Thus, HookA is a novel linker important for dynein-early endosome interaction in vivo.
منابع مشابه
Discovery of a vezatin-like protein for dynein-mediated early endosome transport
Early endosomes are transported bidirectionally by cytoplasmic dynein and kinesin-3, but how the movements are regulated in vivo remains unclear. Here our forward genetic study led to the discovery of VezA, a vezatin-like protein in Aspergillus nidulans, as a factor critical for early endosome distribution. Loss of vezA causes an abnormal accumulation of early endosomes at the hyphal tip, where...
متن کاملFHIP and FTS proteins are critical for dynein-mediated transport of early endosomes in Aspergillus
The minus end-directed microtubule motor cytoplasmic dynein transports various cellular cargoes, including early endosomes, but how dynein binds to its cargo remains unclear. Recently fungal Hook homologues were found to link dynein to early endosomes for their transport. Here we identified FhipA in Aspergillus nidulans as a key player for HookA (A. nidulans Hook) function via a genome-wide scr...
متن کاملMotor proteins Hook on to early endosomes
M any organelles move through the cytoplasm along micro-tubules, pulled back and forth by microtubule-based motor proteins. Early endosomes, for example, are transported by the minus end–directed motor dynein and the plus end–directed motor kinesin-3, which are thought to engage in a " tug of war " with each other as they attempt to haul their cargo in opposite directions. Zhang et al. (1) and ...
متن کاملPeroxisomes move by hitchhiking on early endosomes using the novel linker protein PxdA
Eukaryotic cells use microtubule-based intracellular transport for the delivery of many subcellular cargos, including organelles. The canonical view of organelle transport is that organelles directly recruit molecular motors via cargo-specific adaptors. In contrast with this view, we show here that peroxisomes move by hitchhiking on early endosomes, an organelle that directly recruits the trans...
متن کاملATP-Driven Remodeling of the Linker Domain in the Dynein Motor
Dynein ATPases are the largest known cytoskeletal motors and perform critical functions in cells: carrying cargo along microtubules in the cytoplasm and powering flagellar beating. Dyneins are members of the AAA+ superfamily of ring-shaped enzymes, but how they harness this architecture to produce movement is poorly understood. Here, we have used cryo-EM to determine 3D maps of native flagellar...
متن کامل