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N-cadherin SPRY motifs bind unconventionally-secreted Fbxo45 and regulate multipolar neuron migration

Youn Na, Elif Kon, Hong Cao, Yves Jossin, View ORCID ProfileJonathan A. Cooper
doi: https://doi.org/10.1101/828426
Youn Na
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98019, USA
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Elif Kon
Laboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université catholique de Louvain, 1200 Brussels, Belgium
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Hong Cao
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98019, USA
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Yves Jossin
Laboratory of Mammalian Development & Cell Biology, Institute of Neuroscience, Université catholique de Louvain, 1200 Brussels, Belgium
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Jonathan A. Cooper
Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, 98019, USA
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  • ORCID record for Jonathan A. Cooper
  • For correspondence: jcooper@fhcrc.org
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ABSTRACT

During development of the mammalian neocortex, the orientation of migrating multipolar projection neurons is controlled by Reelin, a secreted glycoprotein, which increases cell-surface expression of N-cadherin. Although N-cadherin regulates cell-cell adhesion, recent results suggest that its adhesive function is not required to orient multipolar neuron migration. To understand N-cadherin function in multipolar migration, we performed two independent screens for embryonic brain proteins that bind the N-cadherin extracellular domain. Both screens detected MycBP2 and SPRY-domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. We found that Fbxo45 is secreted by a non-classical mechanism, not involving a signal peptide and not requiring endoplasmic reticulum to Golgi transport. Secreted Fbxo45 stimulated neurite branching in culture. A SPRY-motif N-cadherin mutant did not bind Fbxo45 and failed to rescue neuron migration even though it still formed trans-homophilic adhesions. The results suggest that secreted Fbxo45 may regulate neurite branching and bind N-cadherin to orient multipolar neuron migration.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted November 01, 2019.
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N-cadherin SPRY motifs bind unconventionally-secreted Fbxo45 and regulate multipolar neuron migration
Youn Na, Elif Kon, Hong Cao, Yves Jossin, Jonathan A. Cooper
bioRxiv 828426; doi: https://doi.org/10.1101/828426
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N-cadherin SPRY motifs bind unconventionally-secreted Fbxo45 and regulate multipolar neuron migration
Youn Na, Elif Kon, Hong Cao, Yves Jossin, Jonathan A. Cooper
bioRxiv 828426; doi: https://doi.org/10.1101/828426

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