Sci. Signal., 22 January 2013
Developmental Neuroscience Signaling Differentiation
L. Bryan Ray
Science, Science Signaling, AAAS, Washington, DC 20005, USA
The six-transmembrane protein GDE2 promotes differentiation through extracellular glycerophosphodiester phosphodiesterase (GDPD) activity and induces neuronal differentiation through inhibition of Notch signaling—a major pathway that maintains stem or progenitor cell states and is implicated in multiple cancers. How then does GDPD activity inhibit Notch signaling, given that GDPD enzymes are known to metabolize glycerophosphodiesters into glycerol-3-phosphate and corresponding alcohols? Park et al. show that the six-transmembrane GDPDs, such as GDE2, do not function as conventional GDPD enzymes but instead cleave the glycosylphosphatidylinositol (GPI) anchors of GPI-anchored proteins. The GDPD activity of GDE2 cleaves and inactivates the GPI-anchored protein RECK, which normally acts to prevent shedding of the Notch ligand Delta. Accordingly, RECK inactivation stimulates Delta shedding leading to Notch inactivation in progenitors and the initiation of cellular differentiation.
S. Park, C. Lee, P. Sabharwal, M. Zhang, C. L. Freel Meyers, S. Sockanathan, GDE2 promotes neurogenesis by glycosylphoshatidylinositol-anchor cleavage of RECK. Science 339, 324–328 (2013). [Abstract] [Full Text]
Citation: L. B. Ray, Signaling Differentiation. Sci. Signal. 6, ec19 (2013).
The editors suggest the following Related Resources on Science sites:
In Science Signaling
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882