Protein kinase A-mediated septin7 phosphorylation disrupts septin filaments and ciliogenesis

Septins are GTP-binding proteins that form heteromeric filaments for proper cell growth and migration. Among these septins, septin7 (SEPT7) is an important component of all septin filaments. Here we showed that protein kinase A (PKA) phosphorylates SEPT7 at Thr197 thus disrupting septin filament dynamics and ciliogenesis. The PKA targeting site at Thr197 of SEPT7 was conserved among species. Treatment of cAMP or overexpression of PKA catalytic subunit (PKACA2) induced SEPT7 phosphorylation. SEPT7 phosphorylation at Thr197 disrupted septin filament formation by reducing SEPT7-SEPT7 interaction, but not affected SEPT7-SEPT6-SEPT2 or SEPT4 interaction. Besides, overexpression of phosphomimetic SEPT7 mutant (T197E) disrupted endogenous SEPT7 filaments suggesting T197E had dominant negative effect on septin filament polymerization. We also identified SEPT7 interacted with the PKACA2 via the GTP-binding domain. Furthermore, PKA-mediated SEPT7 phosphorylation disrupted primary cilia formation. Thus, our data uncover the novel biological function of SEPT7 phosphorylation in septin filament polymerization and primary cilia formation.