POLARIZATION OF MYELINATING SCHWANN-CELL SURFACE-MEMBRANES - ROLE OF MICROTUBULES AND THE TRANS-GOLGI NETWORK

Schwann cells polarize their surface membranes into several biochemica lly 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 dis assembly, confocal microscopy, and electron microscopic immunocytochem istry were used to investigate mechanisms involved in targeting P-o pr otein (P-o), 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 d istributions of Golgi membranes, endoplasmic reticulum, and intermedia te filaments were also altered by colchicine treatment. Electron micro scopic immunocytochemical studies indicated that P-o and MAG are sorte d into separate carrier vesicles as they exit the trans-Golgi network. Following microtubule disassembly, P-o-rich carrier vesicles fused an d formed myelin-like membrane whorls, whereas MAG-rich carrier vesicle s fused and formed mesaxon-like membrane whorls. Microtubule disassemb ly did not result in mistargeting of either P-o or MAG to surface memb ranes. These results indicate that following sorting in the trans-Golg i network, certain carrier vesicles are transported along the myelin i nternode on microtubules; however, microtubules do not appear to targe t these vesicles selectively to specific sites. The targeting of P-o-, MAG-, and laminin-rich carrier vesicles to specific sites most likely occurs by ligand receptor binding mechanisms that permit fusion of ca rrier vesicles only with the appropriate target membrane.