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Journal of Neuroscience, Vol 15, 1797-1807, Copyright © 1995 by Society for Neuroscience
Polarization of myelinating Schwann cell surface membranes: role of microtubules and the trans-Golgi network
BD Trapp, GJ Kidd, P Hauer, E Mulrenin, CA Haney and SB Andrews
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195.
Schwann cells polarize their surface membranes into several biochemically
and ultrastructurally discrete regions of the myelin internode. To form
these membrane domains, Schwann cells must sort, transport, and target
membrane proteins appropriately. In this study, microtubule disassembly,
confocal microscopy, and electron microscopic immunocytochemistry were used
to investigate mechanisms involved in targeting P0 protein (P0), the
myelin-associated glycoprotein (MAG), and laminin to different plasma
membrane domains in myelinating Schwann cells from 35-d-old rat sciatic
nerve. After microtubule disassembly by colchicine, all three proteins
accumulated in Schwann cell perinuclear cytoplasm, indicating that
microtubules are necessary for their transport. The distributions of Golgi
membranes, endoplasmic reticulum, and intermediate filaments were also
altered by colchicine treatment. Electron microscopic immunocytochemical
studies indicated that P0 and MAG are sorted into separate carrier vesicles
as they exit the trans- Golgi network. Following microtubule disassembly,
P0-rich carrier vesicles fused and formed myelin-like membrane whorls,
whereas MAG-rich carrier vesicles fused and formed mesaxon-like membrane
whorls. Microtubule disassembly did not result in mistargeting of either P0
or MAG to surface membranes. These results indicate that following sorting
in the trans-Golgi network, certain carrier vesicles are transported along
the myelin internode on microtubules; however, microtubules do not appear
to target these vesicles selectively to specific sites. The targeting of
P0-, MAG-, and laminin-rich carrier vesicles to specific sites most likely
occurs by ligand receptor binding mechanisms that permit fusion of carrier
vesicles only with the appropriate target membrane.
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