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A new phospholipid phosphatase, PRG-1, is involved in axon growth and regenerative sprouting


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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Figure 1: PRG-1 mRNA expression is brain-specific.
Figure 2: PRG-1 is expressed in cellular processes and in hippocampal neurons.
Figure 3: Developing entorhinal axons are differentially affected by LPA.
Figure 4: PRG-1 protects from LPA-induced retraction.

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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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Correspondence to Robert Nitsch.

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Supplementary information

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).

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