The role of actin polymerization in model Hirano body formation
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Hirano bodies are paracrystalline filamentous actin inclusions associated with multiple neurodegenerative diseases. The mechanism(s) of Hirano body formation remains largely unknown. Model Hirano bodies generated in Dictyostelium were utilized to identify their protein components and formation mechanism. From proteins identified in model Hirano bodies by mass spectrometry, mitochondrial proteins, profilin I and the Arp2/3 complex were further investigated. Mitochondria were not present in model Hirano bodies. Knockdown of profilin I reduces the size of model Hirano bodies. Inhibition of the Arp2/3 complex activity by CK666 reduced model Hirano body formation. When HSPC300, a subunit of an Arp2/3 complex activator, was knocked out, cells could not form model Hirano bodies. In contrast, when WASH, another Arp2/3 complex activator was knocked out, cells formed model Hirano bodies. These findings reveal that de novo actin polymerization is a key aspect of model Hirano body formation.