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  Structural basis of Teneurin-Latrophilin interaction in repulsive guidance of migrating neurons

del Toro, D., Carrasquero-Ordaz, M. A., Chu, A., Ruff, T., Shahin, M., Jackson, V. A., et al. (2020). Structural basis of Teneurin-Latrophilin interaction in repulsive guidance of migrating neurons. Cell, 180(2), 323-339.e19. doi:10.1016/j.cell.2019.12.014.

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 Creators:
del Toro, Daniel1, Author           
Carrasquero-Ordaz, Maria A., Author
Chu, Amy, Author
Ruff, Tobias1, Author           
Shahin, Meriam, Author
Jackson, Verity A., Author
Chavent, Matthieu, Author
Berbeira-Santana, Miguel, Author
Seyit-Bremer, Goenuel1, Author           
Brignani, Sara1, Author           
Kaufmann, Rainer, Author
Lowe, Edward, Author
Klein, Rüdiger1, Author           
Seiradake, Elena, Author
Affiliations:
1Department: Molecules-Signaling-Development / Klein, MPI of Neurobiology, Max Planck Society, ou_1113546              

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Free keywords: PARTICLE MESH EWALD; CELL-CELL ADHESION; ALPHA-LATROTOXIN; IN-VIVO; GENE; EXPRESSION; MECHANISM; RECEPTOR; DYNAMICS; BINDING
 Abstract: Teneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the adhesion GPCR Latrophilin, forming a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, and FLRT proteins are also expressed during murine cortical cell migration at earlier developmental stages. Here, we present crystal structures of Teneurin-Latrophilin complexes that reveal how the lectin and olfactomedin domains of Latrophilin bind across a spiraling beta-barrel domain of Teneurin, the YD shell. We couple structure-based protein engineering to biophysical analysis, cell migration assays, and in utero electroporation experiments to probe the importance of the interaction in cortical neuron migration. We show that binding of Latrophilins to Teneurins and FLRTs directs the migration of neurons using a contact repulsion-dependent mechanism. The effect is observed with cell bodies and small neurites rather than their processes. The results exemplify how a structure-encoded synaptogenic protein complex is also used for repulsive cell guidance.

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Language(s): eng - English
 Dates: 2020-01-23
 Publication Status: Published in print
 Pages: 36
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 Table of Contents: -
 Rev. Type: Peer
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Project name : D.d.T was supported by MINECO/Ramón y Cajal (RYC-2017-23486 and RTI2018-095580-A-I00).
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Funding organization : MINECO

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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 180 (2) Sequence Number: - Start / End Page: 323 - 339.e19 Identifier: ISSN: 0092-8674
CoNE: https://pure.mpg.de/cone/journals/resource/954925463183