A motor for neurofilaments

Neurofilaments modulate the shape and size of neurons. On page 279, Rao et al. describe several lines of evidence demonstrating that neurofilaments interact with the motor protein myosin Va, and that this interaction is critical for proper neurofilament organization. Besides illuminating a poorly understood aspect of neuronal biology, the findings may also help explain the pathogenesis of a debilitating human genetic disease.

In both humans and mice, mutations in the myosin Va gene cause severe defects in skin pigmentation and fatal convulsive disorders. Combining biochemical and genetic approaches, the authors found that the neurofilament light chain is a major ligand of myosin Va in mouse nervous tissue. In mice lacking functional myosin Va, neurofilaments in axons are more densely packed than they are in wild-type mice.

The results suggest that proper neurofilament spacing, and hence normal neuronal shape and function, depends on the dynamic cross-linking of neurofilaments and microfilaments by myosin Va. Myosin Vamight also provide the motive force to move membrane-associated enzymes and receptors along neurofilaments, and to carry out the short-range rearrangements of neurofilaments within the axon that occur during early postnatal development. ▪