Septin 9-containging filaments and Golgi assembly depend on two polybasic domains

Abstract

Septins are GTP-binding proteins involved in several membrane remodeling mechanisms. They associate with membranes, presumably by using a polybasic domain (PB1) that interacts with phosphoinositides (PIs). Membrane-bound septins assemble into microscopic structures that regulate membrane shape. How septins exactly interact with PIs, assemble, and shape membranes is weakly understood. Here, we found that septin 9 has a second polybasic domain (PB2) conserved in the human septin family. Similarly to PB1, PB2 binds specifically to PIs, and both domains are critical for septin filament formation. However, septin 9 membrane association does not depend on these PB domains but on putative PB-adjacent amphipathic helices. The presence of the PB domains guarantees the protein enrichment to PI-contained membranes, which is critical for PI-enriched organelles. In particular, we found that septin 9 PB domains control the assembly and functionality of the Golgi apparatus. Our findings bring novel insights into the role of septins in organelle morphology. HighlightsO_LITwo polybasic domains mediate septin 9 interaction with PIs C_LIO_LIHuman septins have amphipathic helices suitable for binding membrane C_LIO_LISeptin 9 polybasic domains mediate septin high order structure formation C_LIO_LIMutation or depletion of septin polybasic domains induce Golgi fragmentation C_LI