Proteolysis and membrane capture of F-spondin generates combinatorial guidance cues from a single molecule
Open accessAbstract
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.
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Several non-apolipoprotein ligands have been proposed for VLDLR, including Reelin and F-spondin.
“Several non-apolipoprotein ligands have also been proposed for VLDLR, including Reelin2 and F-spondin55.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [55]
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IDOL regulates systemic energy balance through control of neuronal VLDLR expression
Lee, S. D., Priest, C., Bjursell, M., Gao, J., Arneson, D. V., Ahn, I. S., Diamante, G., van Veen, J. E., Massa, M. G., Calkin, A. C., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0127-7 · Cited by 26 · see citing works
- Authors
- Zisman, S., Marom, K., Avraham, O., Rinsky-Halivni, L., Gai, U., Kligun, G., Tzarfaty-Majar, V., Suzuki, T., & Klar, A.
- Affiliations
- Hebrew University of Jerusalem (IL)
- 1Department of Anatomy and Cell Biology, Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel
- Shinshu University (JP)
- Corresponding author
- Klar, Avihu
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-09-17
- Volume
- 178
- Issue
- 7
- Pages
- 1237-1249
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2064656
- OpenAlex
- W2129236727
- Cited by
- 50
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 6
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- F-spondin, proteolysis, floor plate, commissural axon guidance, basement membrane, repulsive guidance cues, ApoER2, LRP4, axon attraction, neuronal network formation
- MeSH terms
- Animals, Basement Membrane, Cell Membrane, Chlorocebus aethiops, Chick Embryo, Chickens, Humans, Models, Biological, Nerve Tissue Proteins, Peptide Fragments, Protein Binding, Protein Processing, Post-Translational, Spinal Cord, Extracellular Matrix Proteins, Neurites, Cell Polarity, Protein Structure, Tertiary, Receptors, Lipoprotein, COS Cells, Protein Transport, LDL-Receptor Related Proteins, Mice, Rats
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