TAAR8 Mediates Increased Migrasome Formation by Cadaverine in RPE Cells

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Migrasomes are novel organelles formed on cell retraction fibers during migration.
• Their roles include intercellular communication, content transfer, and material shedding.
• The molecular mechanisms governing migrasome biogenesis remain largely unelucidated.

Purpose of the Study:

• To investigate the molecular mechanisms of migrasome formation.
• To identify compounds that regulate migrasome activity in retinal pigment epithelial (RPE) cells.

Main Methods:

• Developed a cell line overexpressing GFP-tetraspanin4 for migrasome observation.
• Screened a fecal chemical library to identify migrasome inducers.
• Utilized trace amine-associated receptor 8 (TAAR8) depletion and protein kinase A phosphorylation assays.

Main Results:

• Identified cadaverine, a biogenic amine, as a potent migrasome formation inducer in RPE cells.
• Observed increased migrasome formation with cadaverine and putrescine treatment.
• Demonstrated that TAAR8 depletion inhibits cadaverine-induced migrasome formation.
• Found that cadaverine inhibits protein kinase A phosphorylation.

Conclusions:

• Cadaverine triggers migrasome formation in RPE cells through a TAAR8-mediated pathway.
• This pathway involves the regulation of protein kinase A signaling.
• Elucidates a novel mechanism for migrasome biogenesis and regulation.