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Structure and evolution of neurexophilin
A G Petrenko1, B Ullrich, M Missler
1Howard Hughes Medical Institute, University of Texas Southwestern Medical School, Dallas, Texas 75235, USA.
Summary
We discovered neurexophilin, a novel secreted glycoprotein, which binds to neurexin I alpha. Rodents and cattle express distinct neurexophilin genes, suggesting specialized neuronal functions.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neurexins are crucial cell adhesion molecules in the nervous system.
- The function of specific neurexin-binding partners remains largely unknown.
Purpose of the Study:
- To identify and characterize novel proteins interacting with neurexins.
- To elucidate the structure, gene organization, and expression patterns of a newly identified neurexin-binding protein, neurexophilin.
Main Methods:
- Affinity chromatography using immobilized alpha-latrotoxin.
- Molecular cloning and sequencing of neurexophilin genes from rat, bovine, and mouse.
- Gene expression analysis using RNA blots and in situ hybridization.
- Recombinant protein expression and binding assays.
Main Results:
- A novel 29 kDa protein, neurexophilin, was purified in complex with neurexin I alpha.
- Rat and bovine neurexophilins share homologous C-terminal sequences but differ in N-terminal domains.
- Two distinct neurexophilin genes exist in mice, with differential expression between rodents and cattle.
- Neurexophilin is expressed in a subset of inhibitory interneurons in the adult rat brain, unlike broadly expressed neurexins.
- Neurexophilin is a secreted, N-glycosylated protein that binds to the extracellular domain of neurexin I alpha.
Conclusions:
- Neurexophilin is a secreted glycoprotein synthesized in specific neuronal populations.
- Neurexophilin likely functions as a ligand for neurexins, potentially mediating specific synaptic interactions.