Model of Lis1 function in S. cerevisiae and A. nidulans. (A) In S. cerevisiae, Lis1 (red) is required to recruit dynein (gray) to microtubule plus ends (step 1). Lis1 binding to dynein anchors dynein at the plus end and induces a cargo-ready conformation (step 2). Dynein is then off-loaded to the cortical receptor Num1 (green; step 3). In the absence of Lis1, cortically anchored dynein walks toward the microtubule minus end, biasing movement of the microtubule-attached nucleus into the daughter cell (step 4, green arrow). (B) In A. nidulans hyphae, dynein (gray) is targeted to the microtubule plus end in a Lis1-independent (red), kinesin-1–dependent manner (step 1). Lis1 binding to dynein anchors dynein at the plus end and induces a cargo-ready conformation (step 2). Dynein then binds to endosomes or peroxisomes (green; step 3). In the absence of Lis1, organelle-associated dynein drives retrograde endosome or peroxisome motility (step 4, green arrow).