Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination

Journal article


Kegel, L., Jaegle, M., Driegen, S., Aunin, E., Leslie, K., Fukata, Y., Watanabe, M., Fukata, M. and Meijer, D. 2014. Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination. Development. 141 (8), pp. 1749-1756. https://doi.org/10.1242/dev.107995
AuthorsKegel, L., Jaegle, M., Driegen, S., Aunin, E., Leslie, K., Fukata, Y., Watanabe, M., Fukata, M. and Meijer, D.
Abstract

The cellular interactions that drive the formation and maintenance of the insulating myelin sheath around axons are only partially understood. Leucine-rich glioma-inactivated (LGI) proteins play important roles in nervous system development and mutations in their genes have been associated with epilepsy and amyelination. Their function involves interactions with ADAM22 and ADAM23 cell surface receptors, possibly in apposing membranes, thus attenuating cellular interactions. LGI4-ADAM22 interactions are required for axonal sorting and myelination in the developing peripheral nervous system (PNS). Functional analysis revealed that, despite their high homology and affinity for ADAM22, LGI proteins are functionally distinct. To dissect the key residues in LGI proteins required for coordinating axonal sorting and myelination in the developing PNS, we adopted a phylogenetic and computational approach and demonstrate that the mechanism of action of LGI4 depends on a cluster of three amino acids on the outer surface of the LGI4 protein, thus providing a structural basis for the mechanistic differences in LGI protein function in nervous system development and evolution.

KeywordsEvolution and development, Myelination, Leucine-rich glioma-inactivated, ADAM23 Schwann cell, Mouse
Year2014
JournalDevelopment
Journal citation141 (8), pp. 1749-1756
PublisherThe Company of Biologists
ISSN0950-1991
Digital Object Identifier (DOI)https://doi.org/10.1242/dev.107995
FunderNetherlands Institute for Regenerative Medicine (NIRM)
Netherlands Organisation for Scientific Research (NWO)
European Union
Publication dates
PrintApr 2014
Publication process dates
Deposited22 Oct 2015
Accepted21 Feb 2014
Output statusPublished
Permalink -

https://repository.canterbury.ac.uk/item/877q0/functional-phylogenetic-analysis-of-lgi-proteins-identifies-an-interaction-motif-crucial-for-myelination

  • 18
    total views
  • 0
    total downloads
  • 0
    views this month
  • 0
    downloads this month

Export as

Related outputs

Isolation of functional tubulin dimers and of tubulin-associated proteins from mammalian cells
Yuill, N., Signorile, L., Basu, S., Ottema, S., Lebbink, J., Leslie, K., Smal, I., Dekkers, D., Demmers, J. and Galjart, N. 2016. Isolation of functional tubulin dimers and of tubulin-associated proteins from mammalian cells. Current Biology. 26 (13), pp. 1728-1736. https://doi.org/10.1016/j.cub.2016.04.069