Cytoplasmic protein methylation is essential for neural crest migration

Area of Science:

• Developmental Biology
• Cell Biology
• Biochemistry

Background:

• Neural crest cells are crucial for vertebrate embryonic development, initiating migration early in embryogenesis.
• These cells exhibit enrichment for methylation cycle enzymes like S-adenosylhomocysteine hydrolase (SAHH).
• The role of methylation in neural crest cell migration remains largely unexplored.

Purpose of the Study:

• To investigate the significance of methylation in neural crest cell migration.
• To identify specific methylation-dependent mechanisms governing this process.

Main Methods:

• Assessed the requirement of SAHH for neural crest cell emigration.
• Performed proteomic profiling of cytoplasmic, lysine-methylated proteins in migratory neural crest cells.
• Utilized a methylation-resistant form of elongation factor 1 alpha 1 (EF1α1) to study its functional impact.

Main Results:

• SAHH is essential for the emigration of polarized neural crest cells, confirming methylation's importance in their migration.
• Proteomic analysis identified 182 cytoplasmic, lysine-methylated proteins, with several linked to the cytoskeleton.
• A methylation-resistant EF1α1 variant inhibited neural crest cell migration.

Conclusions:

• Post-translational nonhistone protein methylation plays a novel and essential role in neural crest cell migration.
• Methylation of EF1α1 is a previously unrecognized requirement for efficient neural crest cell migration.