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The Journal of Neuroscience, March 28, 2007, 27(13):3560-3570; doi:10.1523/JNEUROSCI.4926-06.2007

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Development/Plasticity/Repair
Rho Regulates Membrane Transport in the Endocytic Pathway to Control Plasma Membrane Specialization in Oligodendroglial Cells

Angelika Kippert,^1,2 * Katarina Trajkovic,^1,2 * Lawrence Rajendran,⁴ Jonas Ries,³ and Mikael Simons^1,2

¹Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, 37073 Göttingen, Germany, ²Max-Planck-Institute for Experimental Medicine, 37075 Göttingen, Germany, ³Technical University of Dresden, 01062 Dresden, Germany, and ⁴Max-Planck-Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany

Correspondence should be addressed to Dr. Mikael Simons, Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldallee 23, 37073 Göttingen, Germany. Email: msimons{at}gwdg.de

Differentiation of oligodendrocytes is associated with dramatic changes in plasma membrane structure, culminating in the formation of myelin membrane sheaths. Previous results have provided evidence that regulation of endocytosis may represent a mechanism to control myelin membrane growth. Immature oligodendrocytes have a high rate of clathrin-independent endocytosis for the transport of membrane to late endosomes/lysosomes (LE/Ls). After maturation and receiving signals from neurons, endocytosis is reduced and transport of membrane from LE/Ls to the plasma membrane is triggered. Here, we show that changes in Rho GTPase activity are responsible for switching between these two modes of membrane transport. Strikingly, Rho inactivation did not only reduce the transport of cargo to LE/L but also increased the dynamics of LE/L vesicles. Furthermore, we provide evidence that Rho inactivation results in the condensation of the plasma membrane in a polarized manner. In summary, our data reveal a novel role of Rho: to regulate the flow of membrane and to promote changes in cell surface structure and polarity in oligodendroglial cells. We suggest that Rho inactivation is required to trigger plasma membrane specialization in oligodendrocytes.

Key words: oligodendrocytes; neurons; myelin; Rho GTPases; endocytosis; late endosomes/lysosomes

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Received Nov. 13, 2006; revised Feb. 14, 2007; accepted Feb. 20, 2007.

Correspondence should be addressed to Dr. Mikael Simons, Centre for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldallee 23, 37073 Göttingen, Germany. Email: msimons{at}gwdg.de

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