Plk1 relieves centriole block to reduplication by promoting daughter centriole maturation.

Anil Shukla,Jadranka Loncarek,Valentin Magidson,Dong Kong,Meena Sharma

doi:10.1038/ncomms9077

Anil Shukla, Jadranka Loncarek + Show 3 more

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https://doi.org/10.1038/ncomms9077

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Abstract

Centrosome overduplication promotes mitotic abnormalities, invasion and tumorigenesis. Cells regulate the number of centrosomes by limiting centriole duplication to once per cell cycle. The orthogonal orientation between a mother and a daughter centriole, established at the time of centriole duplication, is thought to block further duplication of the mother centriole. Loss of orthogonal orientation (disengagement) between two centrioles during anaphase is considered a licensing event for the next round of centriole duplication. Disengagement requires the activity of Polo-like kinase 1 (Plk1), but how Plk1 drives this process is not clear. Here we employ correlative live/electron microscopy and demonstrate that Plk1 induces maturation and distancing of the daughter centriole, allowing reduplication of the mother centriole even if the original daughter centriole is still orthogonal to it. We find that mother centrioles can undergo reduplication when original daughter centrioles are only ∼80 nm apart, which is the distance centrioles normally reach during prophase.

Highlights

Centrosome overduplication promotes mitotic abnormalities, invasion and tumorigenesis
To describe the earliest ultrastructural changes that occur within the centrosomes during centriole disengagement, we employed correlative live and electron microscopy
Disorientation of a daughter and a mother centriole is currently equated with the loss of centriole block to reduplication, and is thought to be a causative effect of the proteolytic events occurring after metaphase to anaphase transition

Summary

Introduction

Centrosome overduplication promotes mitotic abnormalities, invasion and tumorigenesis. We employ correlative live/electron microscopy and demonstrate that Plk[1] induces maturation and distancing of the daughter centriole, allowing reduplication of the mother centriole even if the original daughter centriole is still orthogonal to it. A cell contains two mature (mother) centrioles, which duplicate in early S forming a new (daughter) centriole in an orthogonal configuration at their proximal end. Disengagement, defined as a loss of orthogonal orientation between centrioles, is thought to occur after anaphase and is considered a licensing event for the round of centriole duplication[3,4]. How Plk[1] drives centriole disengagement is not clear In this manuscript, we employ correlative live-cell electron microscopy to explore Plk1-dependent intra-centrosomal ultrastructural rearrangements leading to the relief of centriole block to reduplication. Our analysis reveals that centriole block to reduplication relies on close spatial association of mother and daughter centrioles, and not on their orthogonal orientation

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