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Published online September 17, 2007
doi:10.1083/jcb.200702184
The Journal of Cell Biology, Vol. 178, No. 7, 1237-1249
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Zisman et al.
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Article

 Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule

Sophie Zisman1, Karen Marom1, Oshri Avraham1, Lilah Rinsky-Halivni1, Uri Gai1, Gilit Kligun1, Vered Tzarfaty-Majar1, Tatsuo Suzuki2, and Avihu Klar1

1 Department of Anatomy and Cell Biology, Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel
2 Department of Neuroplasticity, Institute of Aging and Adaptation, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan

Correspondence to A. Klar: avihu{at}cc.huji.ac.il

The formation of neuronal networks is governed by a limited number of guidance molecules, yet it is immensely complex. The complexity of guidance cues is augmented by posttranslational modification of guidance molecules and their receptors. We report here that cleavage of the floor plate guidance molecule F-spondin generates two functionally opposing fragments: a short-range repellent protein deposited in the membrane of floor plate cells and an adhesive protein that accumulates at the basement membrane. Their coordinated activity, acting respectively as a short-range repellant and a permissive short-range attractant, constricts commissural axons to the basement membrane beneath the floor plate cells. We further demonstrate that the repulsive activity of the inhibitory fragment of F-spondin requires its presentation by the lipoprotein receptor–related protein (LRP) receptors apolipoprotein E receptor 2, LRP2/megalin, and LRP4, which are expressed in the floor plate. Thus, proteolysis and membrane interaction coordinate combinatorial guidance signaling originating from a single guidance cue.

V. Tzarfaty-Majar's present address is Department of Physiology, Hebrew University, Jerusalem 91120, Israel.

Abbreviations used in this paper: ApoER2, apolipoprotein E receptor 2; CMV, cytomegalovirus; E, embryonic day; GPI, glycosylphosphatidylinositol; LRP, lipoprotein receptor–related protein; SCO, subcommissural organ; TSR, thrombospondin type-one repeat; VLDLR, very-low-density lipoprotein receptor.


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