Motor 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 Bielska et al. (2) describe how these motors are recruited to early endosomes by a member of the Hook family of cytoplasmic linker proteins. " A big question in the fi eld is how motors are linked to their cargo, " explains Xin Xiang In 2011, Xiang and colleagues, led by research assistant professor Jun Zhang, discovered that the p25 subunit of the dynactin accessory complex was required to recruit dynein to early endosomes in the fi lamen-tous fungus Aspergillus nidulans (3). " But we didn't know if other proteins were required , " says Xiang, " so we performed a genetic screen to look for additional players. " Zhang et al. screened for Aspergillus mutants that accumulated early endosomes at their hyphal tips, an indicator that dynein is unable to move these organ-elles away from the microtu-bule plus ends concentrated in this part of the cell (1). The researchers focused on mutations that inhibited endosome motil-ity without affecting dynein's function in nuclear distribution. One such mutation was in a gene that the researchers named hookA because it encoded a member of the Hook family of proteins thought to connect organ-elles to the microtubule cytoskeleton. Deleting hookA signifi cantly weakened dynein's interaction with early endosomes, preventing their transport away from the hyphal tip. Hook proteins bind to organelles via their C-terminal domains, and this region of HookA was required for the protein's association with early endosomes. Hook pro-teins' N termini, on the other hand, contain a microtubule-binding domain, but, in the case of the C. elegans Hook protein Zyg-12, this region has also been implicated in binding to dynein (4). Zhang et al. were unable to detect an interaction between HookA and micro-tubules, but the protein's N terminus was important for HookA's association with dynein, an interaction that relied on components of both dynein and dynactin, including p25. " So it's a very complex interaction, " Xiang says. " We still need to fi gure out how HookA interacts with dynein/dynactin and what other proteins …