Polarization of myelinating Schwann cell surface membranes: role of microtubules and the trans-Golgi network.
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.
Trapp
B D
BD
Department of Neurosciences, Cleveland Clinic Foundation, Ohio 44195.
Kidd
G J
GJ
Hauer
P
P
Mulrenin
E
E
Haney
C A
CA
Andrews
S B
SB
D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D007797:Laminin / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000378:metabolism*; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure*; D012584:Sciatic Nerve / Q000378:metabolism / Q000648:ultrastructure
D007797:Laminin; D018993:Myelin P0 Protein; D009185:Myelin Proteins