MODULATION OF THE AXONAL MICROTUBULE CYTOSKELETON BY MYELINATING SCHWANN-CELLS

Trembler PNS myelin-deficient mutant mouse offers a unique model for t he study of axon-glial interactions. Previous work in our laboratory o n Trembler mouse sciatic nerve established that myelinating Schwann ce lls exert a profound effect on the underlying neuronal cytoskeleton. D emyelinated axon segments exhibited decreases in the rate of slow axon al transport, axonal caliber, and neurofilament phosphorylation, as we ll as increases in neurofilament density. The present study considers effects on the microtubule cytoskeleton. At least two aspects of the m icrotubule cytoskeleton in Trembler PNS axons were altered by demyelin ation. First, the stability of the Trembler axonal microtubule cytoske leton is decreased, as measured by decreased levels of insoluble tubul in (Sahenk and Brady, 1987). Second, the composition and phosphorylati on of axonal microtubule-associated proteins, including tau, MAP 1A, a nd MAP 1B, are changed in Trembler demyelinated nerves. Further, the f raction of axonal tubulin moving at slow component b rates was increas ed (de Waegh and Brady 1990, 1991). These results provide further evid ence that cell-cell interactions between myelinating glia and their un derlying axons extend beyond a structural role, actively influencing b iochemical and physiological properties of the axon.