Functional phylogenetic analysis of LGI proteins identifies an interaction motif crucial for myelination
| Autor: | Kris Leslie, Eerik Aunin, Yuko Fukata, Masahiko Watanabe, Martine Jaegle, Masaki Fukata, Dies Meijer, Siska Driegen, Linde Kegel |
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| Přispěvatelé: | Molecular Genetics |
| Rok vydání: | 2014 |
| Předmět: |
Nervous system
Amino Acid Motifs Molecular Sequence Data Schwann cell Nerve Tissue Proteins Biology Mice Structure-Activity Relationship Cell surface receptor Peripheral Nervous System medicine Animals Humans Amino Acid Sequence Amino Acids Molecular Biology Gene Conserved Sequence Myelin Sheath Phylogeny Zebrafish Glycoproteins Genetics chemistry.chemical_classification Sequence Homology Amino Acid Genetic Complementation Test ADAM22 ADAM23 Cell Biology Axons Protein Structure Tertiary Amino acid Cell biology Mice Inbred C57BL ADAM Proteins HEK293 Cells medicine.anatomical_structure nervous system chemistry Organ Specificity Structural Homology Protein Peripheral nervous system Immunology Glycoprotein Protein Binding Developmental Biology |
| Zdroj: | Development, 141(8), 1749-1756. Company of Biologists Ltd Development; Vol 141 |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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