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Published on: December 23, 2022
FEZ2 has acquired additional protein interaction partners relative to FEZ1: functional and evolutionary implications
Marcos R Alborghetti1, Ariane S Furlan, Jörg Kobarg
1Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brasil.
The FEZ2 protein interacts with more proteins than FEZ1, suggesting it compensates for FEZ1's functions and acquires new roles. This explains why FEZ2 can rescue neuronal defects, unlike FEZ1 alone.
Area of Science:
- Neuroscience
- Molecular Biology
- Evolutionary Biology
Background:
- The fasciculation and elongation protein zeta (FEZ) family, including FEZ1 and FEZ2, is crucial for neuronal development.
- UNC-76, a nematode homolog, is essential for axon fasciculation, axonal transport, and axon-axon interactions.
- While FEZ1's function is conserved and can rescue unc-76 mutations, FEZ2's role remains largely unknown.
Purpose of the Study:
- To investigate the evolutionary conservation and divergence of FEZ family proteins.
- To compare the interactome profiles of human FEZ1, FEZ2, and C. elegans UNC-76.
- To elucidate the functional roles of FEZ2 in relation to FEZ1 and UNC-76.
Main Methods:
- Yeast two-hybrid system to analyze protein-protein interactions.
- Comparison of interactome profiles of C-terminal domains of FEZ1, FEZ2, and UNC-76.
- Analysis of the molecular evolution of the FEZ protein family across the animal kingdom.
Main Results:
- FEZ2 interacts with 59 proteins, while FEZ1 interacts with 40 proteins.
- Of the FEZ1 interacting proteins, 90% also interact with UNC-76.
- None of the 19 proteins unique to FEZ2's interactome interact with FEZ1 or UNC-76.
Conclusions:
- FEZ2 exhibits distinct interaction profiles compared to FEZ1 and UNC-76, indicating potential acquisition of new functions.
- The duplication of the unc-76 gene in chordates suggests FEZ2's evolving role.
- FEZ2 likely compensates for the loss of FEZ1 function, explaining the lack of severe phenotypes in FEZ1 knockout mice.
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