page 329. However, the neurons do not have a general endocytosis defect, suggesting a role for Myo6 in specific endocytic events.
Unlike other myosins, Myo6 moves toward the minus ends of actin filaments. Thus, in polarized cells or cell regions, such as the dendritic spines of neurons, Myo6 moves toward the inside of the cell. Dominant-negative mutants of Myo6 have a generalized defect in endocytosis, but this may be explained by Myo6's interaction with AP2, a clathrin adaptor protein, rather than Myo6's normal function.
Osterweil et al. turned instead to Myo6 mutant mice (sv/sv animals). Neurons in the hippocampi of these mice made fewer synaptic connections and had shorter dendritic spines than normal. Additionally, when the researchers stimulated sv/sv neurons in culture with either AMPA or insulin, both of which cause endocytosis of AMPARs, the cells showed less AMPAR internalization than control cells. The sv/sv cells were normal for transferrin endocytosis, suggesting that only specific endocytic targets are affected.
In ongoing work the group finds that only some endocytic events are blocked in other organs of sv/sv animals, suggesting Myo6 may regulate specific endocytosis in a variety of cell types.