SFI1 and centrin form a distal end complex critical for proper centriole architecture and ciliogenesis

Abstract

Over the course of evolution, the function of the centrosome has been conserved in most eukaryotes, but its core architecture has evolved differently in some clades, as illustrated by the presence of centrioles in humans and a spindle pole body in yeast (SPB). Consistently, the composition of these two core elements has diverged greatly, with the exception of centrin, a protein known to form a complex with Sfi1 in yeast to structurally initiate SPB duplication. Even though SFI1 has been localized to human centrosomes, whether this complex exists at centrioles and whether its function has been conserved is still unclear. Here, using conventional fluorescence and super-resolution microscopies, we demonstrate that human SFI1 is a bona fide centriolar protein localizing to the very distal end of the centriole, where it associates with a pool of distal centrin. We also found that both proteins are recruited early during procentriole assembly and that depletion of SFI1 results in the specific loss of the distal pool of centrin, without altering centriole duplication in human cells, in contrast to its function for SPB. Instead, we found that SFI1/centrin complexes are essential for correct centriolar architecture as well as for ciliogenesis. We propose that SFI1/centrin complexes may guide centriole growth to ensure centriole integrity and function as a basal body.

Ultrastructure Expansion Microscopy reveals the nanoscale cellular architecture of budding and fission yeast

“…In addition to Cdc31p, the sole centrin in budding yeast, the SPB half-bridge/bridge also contains Sfi1p (Bouhlel et al, 2015; Burns et al, 2015; Kilmartin, 2003; Li et al, 2006). This core module is critical for SPB duplication in yeast (Bouhlel et al, 2015; Kilmartin, 2003; Li et al, 2006; Rüthnick et al, 2021) while this function does not seem to be conserved in mammals (Bouhlel et al, 2021; Kodani et al, 2019). Immuno-EM analysis as well as SIM microscopy have localized the Sfi1p•Cdc31p complex in S. cerevisiae at the level of the bridge structure (Bestul et al, 2017; Li et al, 2006; Paoletti et al, 2003).…”

“…In addition to Cdc31p, the sole centrin in budding yeast, the SPB halfbridge/bridge also contains Sfi1p (Bouhlel et al, 2015;Burns et al, 2015;Kilmartin, 2003;Li et al, 2006). This core module is critical for SPB duplication in yeast (Bouhlel et al, 2015;Kilmartin, 2003;Li et al, 2006;Rüthnick et al, 2021) while this function does not seem to be conserved in mammals (Bouhlel et al, 2021;Kodani et al, 2019).…”

An Sfi1-like centrin-interacting centriolar plaque protein affects nuclear microtubule homeostasis

“…[55]. In mammals Sfi1 localizes within centrioles and seems implicated in maintaining centriole architecture and cohesion [42]. Centrioles are however missing from the centriolar plaque of asexual blood stage parasites.…”

“…Centrins are a group of calcium binding proteins that are associated with virtually all eukaryotic centrosomes and have been implicated in their duplication [28,38,39]. A key interaction partner of centrin in most organisms is Sfi1 and the presence of an orthologue has been hypothesized for P. falciparum [29,[40][41][42]. Shortly after centrin recruitment the hemispindle collapses, the centrin signal duplicates and the mitotic spindle assembles [34].…”