Journal of Neuroscience, Vol 14, 7440-7450, Copyright © 1994 by Society for Neuroscience
Modulation of the axonal microtubule cytoskeleton by myelinating Schwann cells
LL Kirkpatrick and ST Brady
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas 75235.
The Trembler PNS myelin-deficient mutant mouse offers a unique model for
the study of axon-glial interactions. Previous work in our laboratory on
Trembler mouse sciatic nerve established that myelinating Schwann cells
exert a profound effect on the underlying neuronal cytoskeleton.
Demyelinated axon segments exhibited decreases in the rate of slow axonal
transport, axonal caliber, and neurofilament phosphorylation, as well as
increases in neurofilament density. The present study considers effects on
the microtubule cytoskeleton. At least two aspects of the microtubule
cytoskeleton in Trembler PNS axons were altered by demyelination. First,
the stability of the Trembler axonal microtubule cytoskeleton is decreased,
as measured by decreased levels of insoluble tubulin (Sahenk and Brady,
1987). Second, the composition and phosphorylation of axonal
microtubule-associated proteins, including tau, MAP 1A, and MAP 1B, are
changed in Trembler demyelinated nerves. Further, the fraction of axonal
tubulin moving at slow component b rates was increased (de Waegh and Brady
1990, 1991). These results provide further evidence that cell-cell
interactions between myelinating glia and their underlying axons extend
beyond a structural role, actively influencing biochemical and
physiological properties of the axon.