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Development 137 (14): 2417-2426

RESEARCH ARTICLES

The Adam family metalloprotease Kuzbanian regulates the cleavage of the roundabout receptor to control axon repulsion at the midline

Hope A. Coleman, Juan-Pablo Labrador*, Rebecca K. Chance, and Greg J. Bashaw{dagger}

Department of Neuroscience, University of Pennsylvania School of Medicine, 1113 BRB2/3, 421 Curie Boulevard, Philadelphia, PA 19104, USA

{dagger} Author for correspondence (gbashaw{at}mail.med.upenn.edu)

Accepted for publication 5 May 2010.

Abstract: Slits and their Roundabout (Robo) receptors mediate repulsive axon guidance at the Drosophila ventral midline and in the vertebrate spinal cord. Slit is cleaved to produce fragments with distinct signaling properties. In a screen for genes involved in Slit-Robo repulsion, we have identified the Adam family metalloprotease Kuzbanian (Kuz). Kuz does not regulate midline repulsion through cleavage of Slit, nor is Slit cleavage essential for repulsion. Instead, Kuz acts in neurons to regulate repulsion and Kuz can cleave the Robo extracellular domain in Drosophila cells. Genetic rescue experiments using an uncleavable form of Robo show that this receptor does not maintain normal repellent activity. Finally, Kuz activity is required for Robo to recruit its downstream signaling partner, Son of sevenless (Sos). These observations support the model that Kuz-directed cleavage is important for Robo receptor activation.

Key Words: Axon guidance • Midline • Repulsion • Slit • Robo • Adam • Kuzbanian • Drosophila • Metalloprotease

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