Abstract
Outgrowth of axons in the central nervous system is governed by specific molecular cues. Molecules detected so far act as ligands that bind to specific receptors. Here, we report a new membrane-associated lipid phosphate phosphatase that we have named plasticity-related gene 1 (PRG-1), which facilitates axonal outgrowth during development and regenerative sprouting. PRG-1 is specifically expressed in neurons and is located in the membranes of outgrowing axons. There, it acts as an ecto-enzyme and attenuates phospholipid-induced axon collapse in neurons and facilitates outgrowth in the hippocampus. Thus, we propose a novel mechanism by which axons are able to control phospholipid-mediated signaling and overcome the growth-inhibiting, phospholipid-rich environment of the extracellular space.
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Acknowledgements
The authors thank T. Jöns for help throughout the course of antibody generation; D. Lajko, P. Thiele, M. Petzold, B. Brokowski, E. Bürger and G. Duwe for technical support; S. Lewandowski and D. Wachenschwanz for help with photography and graphic design; K. Rosegger for editorial assistance; and G. Wulczyn, F. Zipp and B. Heimrich for critical remarks on the manuscript. This study was supported by the Deutsche Forschungsgemeinschaft (DFG) SFB 515/A5. N.E.S. is an Investigator of the Charité Medical Research Foundation.
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Supplementary Fig. 1.
Schematic diagram of the proposed axon growth mechanisms in a phospholipid-enriched environment. Axons that are sensitive to a repulsive phospholipid (in this case LPA) but do not express PRG-1 are unable to cross a phospholipid-rich barrier. In contrast, PRG-1-expressing neurons can grow through a phospholipid-rich zone by locally depleting the extracellular pool of repulsive phospholipids acting as ligands on EDG receptors. In this way, PRG-1 may regulate the activation of EDG receptors and thereby modulate axonal outgrowth. Further on, it is hypothesized that other phospholipids than LPA also induce rapid axon collapse and that PRG-1 might be involved in this signaling pathway. (GIF 33 kb)
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Bräuer, A., Savaskan, N., Kühn, H. et al. A new phospholipid phosphatase, PRG-1, is involved in axon growth and regenerative sprouting. Nat Neurosci 6, 572–578 (2003). https://doi.org/10.1038/nn1052
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DOI: https://doi.org/10.1038/nn1052
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