PUBLICATION
Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination
- Authors
- Kegel, L., Jaegle, M., Driegen, S., Aunin, E., Leslie, K., Fukata, Y., Watanabe, M., Fukata, M., Meijer, D.
- ID
- ZDB-PUB-140531-14
- Date
- 2014
- Source
- Development (Cambridge, England) 141: 1749-56 (Journal)
- Registered Authors
- Kegel, Linde
- Keywords
- ADAM23, Evolution and development, Leucine-rich glioma-inactivated, Mouse, Myelination, Schwann cell
- MeSH Terms
-
- Animals
- Molecular Sequence Data
- Amino Acid Sequence
- ADAM Proteins/metabolism
- Structural Homology, Protein
- Conserved Sequence
- Amino Acid Motifs
- Protein Binding
- Amino Acids/metabolism
- Protein Structure, Tertiary
- Zebrafish
- Organ Specificity
- Sequence Homology, Amino Acid
- Mice
- Axons/metabolism
- Structure-Activity Relationship
- Humans
- HEK293 Cells
- Phylogeny*
- Peripheral Nervous System/metabolism
- Nerve Tissue Proteins/metabolism
- Genetic Complementation Test
- Glycoproteins/chemistry*
- Glycoproteins/metabolism*
- Mice, Inbred C57BL
- Myelin Sheath/metabolism*
- PubMed
- 24715463 Full text @ Development
Citation
Kegel, L., Jaegle, M., Driegen, S., Aunin, E., Leslie, K., Fukata, Y., Watanabe, M., Fukata, M., Meijer, D. (2014) Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination. Development (Cambridge, England). 141:1749-56.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping