FA2H controls cool temperature sensing through modifying membrane sphingolipids in Drosophila

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Animals detect ambient temperatures to find optimal environments.
• The molecular mechanisms of cold-sensing are not fully understood.

Purpose of the Study:

• To identify molecules involved in cold-sensing in Drosophila melanogaster.
• To investigate the role of fatty acid 2-hydroxylase (fa2h) in temperature perception.

Main Methods:

• Screening of Drosophila melanogaster Gal4 insertion lines.
• Analysis of fa2h mutants for cool avoidance behavior.
• Calcium imaging of cooling cells (CCs).
• Lipidomic analysis of cell membranes.
• Functional studies in mammalian systems.

Main Results:

• fa2h mutants showed impaired cool avoidance.
• Reintroducing wild-type FA2H in CCs rescued the phenotype.
• fa2h is required for CCs to respond to cool temperatures.
• fa2h mutations decreased 2-hydroxy sphingolipids, increasing membrane fluidity.
• FA2H regulates TRPV4 channel function in mammalian cells.

Conclusions:

• FA2H is essential for cool temperature sensing in Drosophila.
• FA2H impacts neuronal membrane properties and temperature-sensing ion channel function.
• This study reveals a link between membrane lipid composition and thermosensation.