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Antagonistic Coevolution of MER Tyrosine Kinase Expression and Function
Amanda L Evans1, Jack W D Blackburn1, Kyle Taruc1
1Department of Microbiology and Immunology and the Centre for Human Immunology, The University of Western Ontario, London, Canada.
Molecular Biology and Evolution
|April 4, 2017
Summary
Recent evolution of TYRO3, AXL, and MERTK (TAM) receptors shows MERTK
Area of Science:
- Immunology
- Evolutionary Biology
- Molecular Biology
Background:
- TYRO3, AXL, and MERTK (TAM) receptors are crucial for cellular homeostasis and immune responses.
- Defects in TAM receptors are linked to inflammatory and autoimmune diseases.
- Viruses exploit TAM receptors, particularly MERTK, for entry and immune evasion.
Purpose of the Study:
- To investigate the recent evolution of primate TAM receptors.
- To understand how evolutionary changes impact MERTK function and viral interactions.
Main Methods:
- Evolutionary analysis of primate TAM receptor sequences.
- Reconstruction of ancestral MERTK sequences (hominid and primate).
- Analysis of MERTK signal peptide and transmembrane domain mutations.
Main Results:
- Positive selection identified in MERTK's signal peptide and transmembrane domain.
- Human MERTK signal peptide mutations decrease expression via a DNA cruciform motif.
- Human MERTK transmembrane domain substitutions increase self-clustering and avidity.
- Decreased MERTK expression and increased avidity reduce Ebola virus binding.
Conclusions:
- Evolutionary changes in MERTK's signal peptide and transmembrane domain balance expression and avidity.
- These adaptations may represent a defense mechanism against viral hijacking.
- Understanding MERTK evolution offers insights into disease and viral interactions.