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The Journal of Neuroscience, June 15, 2001, 21(12):4290-4298
Repellent Signaling by Slit Requires the Leucine-Rich Repeats
Robin
Battye,
Adrienne
Stevens,
Robert L.
Perry, and
J. Roger
Jacobs
Department of Biology, McMaster University, Hamilton Ontario, L8S
4K1 Canada
Slit is a repellent axon guidance cue produced by the
midline glia in Drosophila that is required to regulate
the formation of contralateral projections and the lateral position of
longitudinal tracts. Four sequence motifs comprise the structure of
Slit: a leucine-rich repeat (LRR), epidermal growth factor-like (EGF) repeats, a laminin-like globular (G)-domain, and a cysteine domain. Here we demonstrate that the LRR is required for repellent signaling and in vitro binding to Robo. Repellent signaling by
slit is reduced by point mutations that encode single
amino acid changes in the LRR domain. By contrast to the EGF or
G-domains, the LRR domain is required in transgenes to affect axon
guidance. Finally, we show that the midline repellent receptor, Robo,
binds Slit proteins with internal deletions that also retain repellent
activity. However, Robo does not bind Slit protein missing the LRR.
Taken together, our data demonstrate that Robo binding and repellent
signaling by Slit require the LRR region.
Key words:
axon guidance; Drosophila; midline glia; Slit; repulsion; Roundabout
Copyright © 2001 Society for Neuroscience 0270-6474/01/21124290-09$05.00/0
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