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

The Journal of Cell Biology
Katarina TrajkovicMikael Simons

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.

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Citations

Aug 27, 2013·Current Genetics·José Miguel MuletLynne Yenush
Oct 23, 2009·Acta Neuropathologica·Monika Bradl, Hans Lassmann
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Methods Mentioned

BETA
transfection
immunoprecipitations
GTPases
GTPase
confocal microscopy
fluorescence microscopy
transfections
PCR
fluorescence imaging
Immunoprecipitation

Software Mentioned

ImageJ
Meta Imaging Series
ScionImage

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