| Cell-cell fusion is important for a number of developmental and physiological processes including fertilization, the immune response, osteogenesis, placenta formation and myogenesis. Drosophila myoblast fusion is an excellent model system for dissecting the molecular and cellular mechanisms of cell-cell fusion. Studies in this model have led to a proposed cellular mechanism whereby actin polymerization generates a protrusive podosome in the fusion competent myoblast (FCM) that promotes fusion pore formation. In contrast, the role of the microtubule cytoskeleton in the context of cell-cell fusion has been understudied. Here I show that the overexpression of the microtubule motor, Khc73, disrupts Drosophila myoblast fusion most likely by aggregating the cell adhesion molecules Dumb-founded (Duf) and Sticks-and-stones (Sns). Furthermore, Khc-73 is required for cell-cell fusion in an in vitro cell culture model. Khc-73 appears to be partially redundant with the other kinesin-3 family members because knockdown of the entire family generates a stronger cell-cell fusion defect than knockdown of only Khc-73 in the in vitro cell culture model. When expressed in S2 cells Khc-73 accumulates at the plus ends of microtubules, where it co-localizes with overexpressed Sns. Khc-73 accumulation requires both the motor and CAP-GLY domain of Khc-73. Based on total internal reflection (TIRF) microscopy, the motor domain is required for efficient movement, while the CAP-GLY domain is required for plus-end accumulation. Interestingly, plus-end accumulation of Khc-73 requires the Drosophila homolog of WASp-interacting protein (WIP), Solitary (Sltr). Sltr is required for the generation of the invasive podosome during myoblast fusion. Taken together, these results suggest a model where Khc-73 is involved in polarized trafficking of the cell adhesion molecules Duf and Sns and in maintaining cell cortical polarity through its interaction with Sltr. |
