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First published online 26 February 2008
doi: 10.1242/jcs.022731


Journal of Cell Science 121, 834-842 (2008)
Published by The Company of Biologists 2008
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Research Article

Distinct endocytic recycling of myelin proteins promotes oligodendroglial membrane remodeling

Christine Winterstein, Jacqueline Trotter and Eva-Maria Krämer-Albers*

Department of Biology, Unit of Molecular Cell Biology, University of Mainz, Bentzelweg 3, 55128 Mainz, Germany

* Author for correspondence (e-mail: emkraemer{at}uni-mainz.de)

Accepted 20 December 2007

The central nervous system myelin sheath is a multilayered specialized membrane with compacted and non-compacted domains of defined protein composition. How oligodendrocytes regulate myelin membrane trafficking and establish membrane domains during myelination is largely unknown. Oligodendroglial cells respond to neuronal signals by adjusting the relative levels of endocytosis and exocytosis of the major myelin protein, proteolipid protein (PLP). We investigated whether endocytic trafficking is common to myelin proteins and analyzed the endocytic fates of proteins with distinct myelin subdomain localization. Interestingly, we found that PLP, myelin-associated glycoprotein (MAG) and myelin-oligodendrocyte glycoprotein (MOG), which localize to compact myelin, periaxonal loops and abaxonal loops, respectively, exhibit distinct endocytic fates. PLP was internalized via clathrin-independent endocytosis, whereas MAG was endocytosed by a clathrin-dependent pathway, although both proteins were targeted to the late-endosomal/lysosomal compartment. MOG was also endocytosed by a clathrin-dependent pathway, but in contrast to MAG, trafficked to the recycling endosome. Endocytic recycling resulted in the association of PLP, MAG and MOG with oligodendroglial membrane domains mimicking the biochemical characteristics of myelin domains. Our results suggest that endocytic sorting and recycling of myelin proteins may assist plasma membrane remodeling, which is necessary for the morphogenesis of myelin subdomains.

Key words: Endocytosis, Recycling, Membrane remodeling, Oligodendrocytes, Myelin domains


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