A CONVENTIONAL MYOSIN MOTOR-DRIVES NEURITE OUTGROWTH

Neuritic outgrowth is a striking example of directed motility, powered through the actions of molecular motors. Members of the myosin superf amily of actin-associated motors have been implicated in this complex process. Although conventional myosin II is known to be present in neu rons,where it is localized at the leading edge of growth cones and in the cell cortex close to the plasma membrane, its functional involveme nt in growth cone motility has remained unproven. Here, we show that a ntisense oligodeoxyribonucleotides, complementary to a specific isofor m of conventional myosin (myosin IIB), attenuate filopodial extension whereas sense and scrambled control oligodeoxyribonucleotides have no effect. Attenuation is shown to be reversible, neurite outgrowth being restored after cessation of the antisense regimen. Myosin IIB mRNA wa s present during active neurite extension, but levels were minimal in phenotypically rounded cells before neurite outgrowth and message leve ls decreased during antisense treatment. By contrast, the myosin IIA i soform is shown to be expressed constitutively both before and during neurite outgrowth and throughout exposure to myosin IIB antisense olig odeoxyribonucleotides. These results provide direct evidence that a co nventional two-headed myosin is required for growth cone motility and is responsible, at least in part, for driving neuritic process outgrow th.