An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly

McLamarrah, Tiffany A.; Buster, Daniel W.; Galletta, Brian J.; Boese, Cody J.; Ryniawec, John M.; Hollingsworth, Natalie A; Byrnes, Amy E.; Brownlee, Christopher; Slep, Kevin C.; Rusan, Nasser M.; Rogers, Gerald S.

doi:10.1083/jcb.201605106

Cited by 49 publications

(73 citation statements)

References 53 publications

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“…Drosophila Ana2 does not require direct binding to Plk4 for its recruitment to procentrioles (McLamarrah et al, 2018). However, centriole recruitment of Ana2/STIL does require Plk4 kinase activity as well as phosphorylation of Ana2’s N terminus (Moyer et al, 2015; Dzhindzhev et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

“…Based on the finding that deletion of the central coiled-coil in Ana2 prevents Plk4 binding and targeting to centrioles (Ohta et al, 2014; Arquint et al, 2015; Kratz et al, 2015; Moyer et al, 2015), it has been proposed that a direct interaction with Plk4 mediates Ana2 loading onto centrioles. However, we have shown that coiled-coil deletion actually has multiple deleterious effects because it also disrupts Ana2’s ability to oligomerize and interact with Sas4 (McLamarrah et al, 2018). By using a separation-of-function phosphomimetic (PM) mutation in Ana2 that is unable to bind Plk4, we observed that PM Ana2 localizes properly to the procentriole assembly site (McLamarrah et al, 2018), suggesting that Ana2 recruitment relies on a mechanism independent of Plk4 binding.…”

Section: Introductionmentioning

confidence: 99%

“…1 A; Stevens et al, 2010; Tang et al, 2011; Vulprecht et al, 2012; Cottee et al, 2013; Hatzopoulos et al, 2013). Through interactions with its coiled-coil and C terminus, Ana2/STIL binds Plk4 (Dzhindzhev et al, 2014; Ohta et al, 2014, 2018; Kratz et al, 2015; McLamarrah et al, 2018), and activates the kinase, possibly by relieving Plk4 autoinhibition (Klebba et al, 2015; Arquint et al, 2015; Moyer et al, 2015). In turn, Ana2/STIL is extensively phosphorylated (Dzhindzhev et al, 2014; Ohta et al, 2014; Kratz et al, 2015), which occurs in an ordered pattern (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In turn, Ana2/STIL is extensively phosphorylated (Dzhindzhev et al, 2014; Ohta et al, 2014; Kratz et al, 2015), which occurs in an ordered pattern (Fig. 1 A; McLamarrah et al, 2018). Initially, phosphorylation predominantly occurs in the N terminus, which promotes Ana2 recruitment to the procentriole assembly site (Dzhindzhev et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Subsequently, phosphorylation of the STAN domain generates a phospho-binding site for the cartwheel protein, Sas6, a critical step required for Sas6 procentriole loading (Dzhindzhev et al, 2014; Ohta et al, 2014; Kratz et al, 2015; Moyer et al, 2015). Last, phosphorylation of the Ana2 central region releases Plk4 (McLamarrah et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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A molecular mechanism for the procentriole recruitment of Ana2

McLamarrah

Speed

Ryniawec

et al. 2019

Journal of Cell Biology

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During centriole duplication, a preprocentriole forms at a single site on the mother centriole through a process that includes the hierarchical recruitment of a conserved set of proteins, including the Polo-like kinase 4 (Plk4), Ana2/STIL, and the cartwheel protein Sas6. Ana2/STIL is critical for procentriole assembly, and its recruitment is controlled by the kinase activity of Plk4, but how this works remains poorly understood. A structural motif called the G-box in the centriole outer wall protein Sas4 interacts with a short region in the N terminus of Ana2/STIL. Here, we show that binding of Ana2 to the Sas4 G-box enables hyperphosphorylation of the Ana2 N terminus by Plk4. Hyperphosphorylation increases the affinity of the Ana2–G-box interaction, and, consequently, promotes the accumulation of Ana2 at the procentriole to induce daughter centriole formation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A molecular mechanism for the procentriole recruitment of Ana2

McLamarrah

Speed

Ryniawec

et al. 2019

Journal of Cell Biology

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Nine‐fold symmetry of centriole: The joint efforts of its core proteins

Tian

Yan

2022

BioEssays

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The centriole is a widely conserved organelle required for the assembly of centrosomes, cilia, and flagella. Its striking feature – the nine‐fold symmetrical structure, was discovered over 70 years ago by transmission electron microscopy, and since elaborated mostly by cryo‐electron microscopy and super‐resolution microscopy. Here, we review the discoveries that led to the current understanding of how the nine‐fold symmetrical structure is built. We focus on the recent findings of the centriole structure in high resolution, its assembly pathways, and its nine‐fold distributed components. We propose a model that the assembly of the nine‐fold symmetrical centriole depends on the concerted efforts of its core proteins. Also see the video abstract here: https://youtu.be/m4h_3II_WJo

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Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis

Duan

Srikantha

Amoiroglou

et al. 2023

Cell. Mol. Life Sci.

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Barrier-to-autointegration factor (BAF/BANF) is a nuclear lamina protein essential for nuclear integrity, chromatin structure, and genome stability. Whereas complete loss of BAF causes lethality in multiple organisms, the A12T missense mutation of the BANF1 gene in humans causes a premature aging syndrome, called Néstor-Guillermo Progeria Syndrome (NGPS). Here, we report the first in vivo animal investigation of progeroid BAF, using CRISPR editing to introduce the NGPS mutation into the endogenous Drosophila baf gene. Progeroid BAF adults are born at expected frequencies, demonstrating that this BAF variant retains some function. However, tissue homeostasis is affected, supported by studies of the ovary, a tissue that depends upon BAF for stem cell survival and continuous oocyte production. We find that progeroid BAF causes defects in germline stem cell mitosis that delay anaphase progression and compromise chromosome segregation. We link these defects to decreased recruitment of centromeric proteins of the kinetochore, indicating dysfunction of cenBAF, a localized pool of dephosphorylated BAF produced by Protein Phosphatase PP4. We show that DNA damage increases in progenitor germ cells, which causes germ cell death due to activation of the DNA damage transducer kinase Chk2. Mitotic defects appear widespread, as aberrant chromosome segregation and increased apoptosis occur in another tissue. Together, these data highlight the importance of BAF in establishing centromeric structures critical for mitosis. Further, these studies link defects in cenBAF function to activation of a checkpoint that depletes progenitor reserves critical for tissue homeostasis, aligning with phenotypes of NGPS patients.

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An ordered pattern of Ana2 phosphorylation by Plk4 is required for centriole assembly

Abstract: Centriole duplication is tightly regulated throughout the cell cycle to ensure one duplication event per centriole. McLamarrah et al. show that a stepwise pattern of Ana2 phosphorylation by Plk4 facilitates proper centriole duplication.

Cited by 49 publications

References 53 publications

A molecular mechanism for the procentriole recruitment of Ana2

A molecular mechanism for the procentriole recruitment of Ana2

Nine‐fold symmetry of centriole: The joint efforts of its core proteins

Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis

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