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J. Cell Biol. 172 (6): 937-948

Copyright © 2006 by the Rockefeller University Press.


Article

Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites

Katarina Trajkovic1,2, Ajit Singh Dhaunchak2, José T. Goncalves2, Dirk Wenzel1, Anja Schneider1,2, Gertrude Bunt2, Klaus-Armin Nave2, , and Mikael Simons1,2

1 Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, 37073 Göttingen, Germany
2 Max-Planck-Institute for Experimental Medicine, 37075 Göttingen, Germany

Correspondence to M. Simons: msimons{at}gwdg.de

Abstract: During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. Neuron-derived signaling molecules are temporally and spatially required to coordinate oligodendrocyte differentiation. In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. These findings reveal a fundamental and novel role of LEs/Ls in oligodendrocytes: to store and release PLP in a regulated fashion. The release of myelin membrane from LEs/Ls by neuronal signals may represent a mechanism to control myelin membrane growth.

K. Trajkovic and A.S. Dhaunchak contributed equally to this paper.

Abbreviations used in this paper: LE/L, late endosome/lysosome; mßCD, methyl-ß-cyclodextrin; MHC, major histocompatibility complex; PLP, proteolipid protein; TIRFM; total internal reflection fluorescence microscopy.


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