Sub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold

Schweizer, Nina; Haren, Laurence; Dutto, Ilaria; Viais, Ricardo; Lacasa, Cristina; Merdes, Andreas; Lüders, Jens

doi:10.1038/s41467-021-26252-5

Cited by 36 publications

(53 citation statements)

References 99 publications

(139 reference statements)

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“…We measured the lateral distribution of LRRCC1 signal intensity peak relative to the long axis of the centriole. The distance between peaks was greater for LRRCC1 than for hPOC5, a marker that localizes symmetrically in the centriole ( Azimzadeh et al, 2009 ; Le Guennec et al, 2020 ; Schweizer et al, 2021 ), confirming the asymmetry of LRRCC1 staining. The distal pattern obtained by U-ExM showed some variability, especially in the distance between LRRCC1 and the centriole wall ( Figure 1c ), which could result from the fact that centrioles were not perfectly orthogonal to the imaging plan.…”

Section: Resultssupporting

confidence: 52%

Evolutionary conservation of centriole rotational asymmetry in the human centrosome

Gaudin

Gil

Boumendjel

et al. 2022

eLife

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Centrioles are formed by microtubule triplets in a nine-fold symmetric arrangement. In flagellated protists and in animal multiciliated cells, accessory structures tethered to specific triplets render the centrioles rotationally asymmetric, a property that is key to cytoskeletal and cellular organization in these contexts. In contrast, centrioles within the centrosome of animal cells display no conspicuous rotational asymmetry. Here, we uncover rotationally asymmetric molecular features in human centrioles. Using ultrastructure expansion microscopy, we show that LRRCC1, the ortholog of a protein originally characterized in flagellate green algae, associates preferentially to two consecutive triplets in the distal lumen of human centrioles. LRRCC1 partially co-localizes and affects the recruitment of another distal component, C2CD3, which also has an asymmetric localization pattern in the centriole lumen. Together, LRRCC1 and C2CD3 delineate a structure reminiscent of a filamentous density observed by electron microscopy in flagellates, termed the 'acorn'. Functionally, the depletion of LRRCC1 in human cells induced defects in centriole structure, ciliary assembly and ciliary signaling, supporting that LRRCC1 cooperates with C2CD3 to organizing the distal region of centrioles. Since a mutation in the LRRCC1 gene has been identified in Joubert syndrome patients, this finding is relevant in the context of human ciliopathies. Taken together, our results demonstrate that rotational asymmetry is an ancient property of centrioles that is broadly conserved in human cells. Our work also reveals that asymmetrically localized proteins are key for primary ciliogenesis and ciliary signaling in human cells.

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Section: Resultssupporting

confidence: 52%

Evolutionary conservation of centriole rotational asymmetry in the human centrosome

Gaudin

Gil

Boumendjel

et al. 2022

eLife

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“…We also noted that organization of gamma-tubulin at the PCM was disrupted while its pool at the centriole wall and lumen remained intact(Fig. S6C), which was recently reported to be required for centriole integrity and cilium assembly (Schweizer et al, 2021).…”

Section: Resultssupporting

confidence: 66%

The ciliopathy protein CCDC66 controls mitotic progression and cytokinesis by promoting microtubule nucleation and organization

Batman

Deretic

Fırat-Karalar

2022

Preprint

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Precise spatiotemporal control of microtubule nucleation and organization is critical for faithful segregation of cytoplasmic and genetic material during cell division and signaling via the primary cilium in quiescent cells. Microtubule-associated proteins (MAPs) govern assembly, maintenance, and remodeling of diverse microtubule arrays. While a set of conserved MAPs are only active during cell division, an emerging group of MAPs acts as dual regulators in dividing and non-dividing cells. Here, we elucidated the nonciliary functions and molecular mechanism of action of the ciliopathy-linked protein CCDC66, which we previously characterized as a regulator of ciliogenesis in quiescent cells. We showed that CCDC66 dynamically localizes to the spindle poles, the bipolar spindle, the spindle midzone, the central spindle and the midbody in dividing cells and interacts with the core machinery of centrosome maturation and MAPs involved in cell division. Loss-of-function experiments revealed its functions during mitotic progression and cytokinesis. Specifically, CCDC66 depletion resulted in defective spindle assembly and positioning, kinetochore fiber stability, chromosome alignment in metaphase as well as central spindle and midbody assembly and organization in anaphase and cytokinesis. Notably, CCDC66 regulates mitotic microtubule nucleation via noncentrosomal and centrosomal pathways via recruitment of gamma-tubulin to the spindle poles and the spindle. Additionally, CCDC66 bundles microtubules in vitro and in cells by its C-terminal microtubule-binding domain. Phenotypic rescue experiments showed that the microtubule and centrosome-associated pools of CCDC66 individually or cooperatively mediate its mitotic and cytokinetic functions. Collectively, our findings identify CCDC66 as a multifaceted regulator of the nucleation and organization of the diverse mitotic and cytokinetic microtubule arrays and provides new insight into nonciliary defects that underlie ciliopathies.

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“…Acetylated tubulin labeling showed cylindrical structures with the dimensions of normal centrioles, some with orthogonally positioned procentrioles, identified from their shorter length (Figure 4A). All centrioles had associated γ -tubulin, both in pericentriolar distribution and in the lumen, as expected for centrioles that have matured to become centrosomes and functional MTOCs (Schweizer et al, 2021).…”

Section: Resultsmentioning

confidence: 53%

Post-mitotic centriole disengagement and maturation leads to centrosome amplification in polyploid trophoblast giant cells

Buss

Stratton

Milenković

et al. 2022

Preprint

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DNA replication is normally coupled with centriole duplication in the cell cycle. Trophoblast giant cells (TGCs) of the placenta undergo endocycles resulting in polyploidy but their centriole state is not known. We used a cell culture model for TGC differentiation to examine centriole and centrosome number and properties. Prior to differentiation, trophoblast stem cells (TSCs) have either two centrioles before duplication, or four centrioles after. We find that average nuclear area increases approximately 8-fold over differentiation, but most TGCs do not have more than four centrioles. However, these centrioles become disengaged, acquire centrosome proteins, and can nucleate microtubules. In addition, some TGCs undergo further duplication and disengagement of centrioles, resulting in substantially higher numbers. Live imaging revealed that disengagement and separation are centriole autonomous and can occur asynchronously. Centriole amplification, when present, occurs by the standard mechanism of one centriole generating one procentriole. PLK4 inihibition blocks centriole formation in differentiating TGCs but does not affect endocycle progression. In summary, centrioles in TGC endocycles undergo disengagement and conversion to centrosomes. This increases centrosome number, but to a limited extent compared with DNA reduplication.

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Sub-centrosomal mapping identifies augmin-γTuRC as part of a centriole-stabilizing scaffold

Cited by 36 publications

References 99 publications

Evolutionary conservation of centriole rotational asymmetry in the human centrosome

Evolutionary conservation of centriole rotational asymmetry in the human centrosome

The ciliopathy protein CCDC66 controls mitotic progression and cytokinesis by promoting microtubule nucleation and organization

Post-mitotic centriole disengagement and maturation leads to centrosome amplification in polyploid trophoblast giant cells

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