Interaction between the<i>Caenorhabditis elegans</i>centriolar protein SAS-5 and microtubules facilitates organelle assembly

Bianchi, Sarah; Rogala, Kacper B.; Dynes, Nicola J.; Hilbert, Manuel; Leidel, Sebastian A.; Steinmetz, Michel O.; Gönczy, Pierre; Vakonakis, Ioannis

doi:10.1091/mbc.e17-06-0412

Cited by 8 publications

(11 citation statements)

References 84 publications

(131 reference statements)

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“…Indeed, multiple lines of evidence indicate that phosphorylation of STIL by PLK4 increases centriolar retention of STIL-PLK4 complexes ( Lambrus et al., 2015 , Moyer et al., 2015 , Ohta et al., 2018 , Vulprecht et al., 2012 , Zitouni et al., 2016 ). This PLK4-activity-dependent anchoring effect is likely to be mediated largely by the interaction of STIL with SAS6 complexes, but it could also be enhanced by the interactions of phosphorylated STIL with other centriolar proteins and microtubules ( Bianchi et al., 2018 , Ohta et al., 2018 ). Therefore, we postulate the existence of a positive feedback loop in which PLK4 activity autoamplifies itself by strengthening its centriolar anchoring and, therefore, increasing its spatial density.…”

Section: Resultsmentioning

confidence: 99%

Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network

2018

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SummaryCentrioles, the cores of centrosomes and cilia, duplicate every cell cycle to ensure their faithful inheritance. How only a single procentriole is produced on each mother centriole remains enigmatic. We propose the first mechanistic biophysical model for procentriole initiation which posits that interactions between kinase PLK4 and its activator-substrate STIL are central for procentriole initiation. The model recapitulates the transition from a uniform “ring” of PLK4 surrounding the mother centriole to a single PLK4 “spot” that initiates procentriole assembly. This symmetry breaking requires autocatalytic activation of PLK4 and enhanced centriolar anchoring of PLK4 by phosphorylated STIL. We find that in situ degradation of active PLK4 cannot break symmetry. The model predicts that competition between transient PLK4 activity maxima for PLK4-STIL complexes destabilizes the PLK4 ring and produces instead a single PLK4 spot. Weakening of competition by overexpression of PLK4 and STIL causes progressive addition of supernumerary procentrioles, as observed experimentally.

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Section: Resultsmentioning

confidence: 99%

Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network

2018

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“…Moreover, the SAS-4/CPAP TCP domain is required for the incorporation of SAS-4 into the centriole in C. elegans . SAS-5 has also been shown to bind to microtubules through a region that overlaps with the SAS-4 binding domain, suggesting that the interaction of SAS-5 with microtubules and SAS-4 may be mutually exclusive (Bianchi et al, 2018). In the future, it will be interesting to investigate if ZYG-1/PLK4 kinase activity regulates the critical SAS-5/SAS-4 interaction in C. elegans by switching SAS-5 from binding microtubules to an association with SAS-4.…”

Section: Discussionmentioning

confidence: 99%

PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole cartwheel to the microtubule wall

Moyer

Holland

2019

eLife

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Centrioles play critical roles in organizing the assembly of the mitotic spindle and templating the formation of primary cilia. Centriole duplication occurs once per cell cycle and is regulated by Polo-like kinase 4 (PLK4). Although significant progress has been made in understanding centriole composition, we have limited knowledge of how PLK4 activity controls specific steps in centriole formation. Here, we show that PLK4 phosphorylates its centriole substrate STIL on a conserved site, S428, to promote STIL binding to CPAP. This phospho-dependent binding interaction is conserved in Drosophila and facilitates the stable incorporation of both STIL and CPAP into the centriole. We propose that procentriole assembly requires PLK4 to phosphorylate STIL in two different regions: phosphorylation of residues in the STAN motif allow STIL to bind SAS6 and initiate cartwheel assembly, while phosphorylation of S428 promotes the binding of STIL to CPAP, linking the cartwheel to microtubules of the centriole wall.

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“…MT binding requires SAS-5 oligomerization and a disordered protein segment that overlaps with the SAS-4 binding site. SAS-5-MT interaction facilitates centriole assembly (Bianchi et al, 2018). CEP295 (centrosomal protein 295) is recruited to the proximal end of procentrioles in early S-phase when it is localized at the centriolar MT wall which surrounds the human SAS6 cartwheel hub.…”

Section: Mt In Cell Divisionmentioning

confidence: 99%

Microtubules: From understanding their dynamics to using them as potential therapeutic targets

Ilan

2018

Journal Cellular Physiology

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Microtubules (MT) and actin microfilaments are dynamic cytoskeleton components involved in a range of intracellular processes. MTs play a role in cell division, beating of cilia and flagella, and intracellular transport. Over the past decades, much knowledge has been gained regarding MT function and structure, and its role in underlying disease progression. This makes MT potential therapeutic targets for various disorders. Disturbances in MT and their associated proteins are the underlying cause of diseases such as Alzheimer’s disease, cancer, and several genetic diseases. Some of the advances in the field of MT research, as well as the potenti G beta gamma, is needed al uses of MT‐targeting agents in various conditions have been reviewed here.

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Interaction between theCaenorhabditis eleganscentriolar protein SAS-5 and microtubules facilitates organelle assembly

Cited by 8 publications

References 84 publications

Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network

Autoamplification and Competition Drive Symmetry Breaking: Initiation of Centriole Duplication by the PLK4-STIL Network

PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole cartwheel to the microtubule wall

Microtubules: From understanding their dynamics to using them as potential therapeutic targets

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