Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 339 (6117): 324-328

Copyright © 2013 by the American Association for the Advancement of Science

GDE2 Promotes Neurogenesis by Glycosylphosphatidylinositol-Anchor Cleavage of RECK

Sungjin Park,1,* Changhee Lee,1,* Priyanka Sabharwal,1 Mei Zhang,1 Caren L. Freel Meyers,2 Shanthini Sockanathan1,{dagger}

Abstract: The six-transmembrane protein glycerophosphodiester phosphodiesterase 2 (GDE2) induces spinal motor neuron differentiation by inhibiting Notch signaling in adjacent motor neuron progenitors. GDE2 function requires activity of its extracellular domain that shares homology with glycerophosphodiester phosphodiesterases (GDPDs). GDPDs metabolize glycerophosphodiesters into glycerol-3-phosphate and corresponding alcohols, but whether GDE2 inhibits Notch signaling by this mechanism is unclear. Here, we show that GDE2, unlike classical GDPDs, cleaves glycosylphosphatidylinositol (GPI) anchors. GDE2 GDPD activity inactivates the Notch activator RECK (reversion-inducing cysteine-rich protein with kazal motifs) by releasing it from the membrane through GPI-anchor cleavage. RECK release disinhibits ADAM (a disintegrin and metalloproteinase) protease-dependent shedding of the Notch ligand Delta-like 1 (Dll1), leading to Notch inactivation. This study identifies a previously unrecognized mechanism to initiate neurogenesis that involves GDE2-mediated surface cleavage of GPI-anchored targets to inhibit Dll1-Notch signaling.

1 Solomon Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, PCTB1004, 725 N Wolfe Street, Baltimore, MD 21205, USA.
2 Department of Pharmacology and Molecular Sciences, School of Medicine, Johns Hopkins University, WBSB 301A, 725 N Wolfe Street, Baltimore, MD 21205, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ssockan1{at}

High NaCl- and urea-induced posttranslational modifications that increase glycerophosphocholine by inhibiting GDPD5 phosphodiesterase.
S. Topanurak, J. D. Ferraris, J. Li, Y. Izumi, C. K. Williams, M. Gucek, G. Wang, X. Zhou, and M. B. Burg (2013)
PNAS 110, 7482-7487
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882