Abstract
During centriole duplication, a single daughter centriole is formed next to the mother centriole. The molecular mechanism that determines a single duplication site remains a long-standing question. Here, we show that intrinsic self-organization of Plk4 is implicated in symmetry breaking in the process of centriole duplication. We demonstrate that Plk4 has an ability to phase-separate into condensates via an intrinsically disordered linker and that the condensation properties of Plk4 are regulated by autophosphorylation. Consistently, the dissociation dynamics of centriolar Plk4 are controlled by autophosphorylation. We further found that autophosphorylated Plk4 is already distributed as a single focus around the mother centriole before the initiation of procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. Perturbation of Plk4 self-organization affects the asymmetry of centriolar Plk4 distribution and proper centriole duplication. Overall, we propose that the spatial pattern formation of Plk4 is a determinant of a single duplication site per mother centriole.
Highlights
During centriole duplication, a single daughter centriole is formed next to the mother centriole
While performing in vitro biochemical experiments, we unexpectedly found that a kinase-dead (KD) mutant of a purified Plk[4] fragment (Kinase + Linker 1) was highly insoluble compared with wild-type (WT) (Fig. 1a, b, Supplementary Fig. 1a)
We demonstrated that Plk[4] has an ability to selfassemble into dynamic or less dynamic condensates depending on its autophosphorylation state and that condensation properties of Plk[4] are implicated in the regulation of centriole copy number
Summary
A single daughter centriole is formed next to the mother centriole. We further found that autophosphorylated Plk[4] is already distributed as a single focus around the mother centriole before the initiation of procentriole formation, and is subsequently targeted for STIL-HsSAS6 loading. The mechanism by which the local amount and/ or the kinase activity of Plk[4] at mother centrioles are coordinated to ensure formation of a single daughter centriole on a mother centriole remains elusive. We show that the occurrence of Plk[4] activation is already detectable before STIL-HsSAS6 loading into a single site around the mother centriole These findings imply that self-condensation and autonomous activation of Plk[4] are implicated in the determination of a site for STIL-HsSAS6 loading to trigger daughter centriole formation
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