Search

Multifocal flat illumination for field-independent imaging (mfFIFI) enables patterned illumination over an extended field of view. Integration with instant structured illumination microscope allowed for high-speed, multicolor, volumetric super-resolution imaging over 100 × 100 µm².

Centrioles are formed from a nine-fold symmetric cartwheel structure. Using mutants of the cartwheel protein SAS-6, which alters cartwheel symmetry, Hirono, Gönczy, Steinmetz and colleagues show that the microtubule wall also determines centriole shape.

This Review discusses recent advances that shed new light on the relationship between centrosomes and cancer, raising the possibility that centrosome aberrations contribute to this disease in different ways than initially envisaged.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

The centriole is crucial for fundamental cellular processes in eukaryotes, including cell polarity, signalling and motility. This Review discusses recent insights into the molecular architecture of centrioles and the principles governing their assembly, with a focus on human cells.

The centriole is crucial for the formation of flagella, cilia and centrosomes. The ultrastructure of the centriole reveals a striking ninefold radial arrangement of microtubules. Emerging insights into the molecular mechanisms of centriole assembly include the function of spindle assembly abnormal 6 (SAS-6) proteins in imparting the ninefold symmetry.

Microtubules carry patterns of post-translational modifications that are important for the regulation of key cellular processes. Now a semi-synthetic method facilitates the production of tubulins with defined post-translational modifications. Using these designer tubulins, polyglutamylation of α-tubulin is found to promote its detyrosination by enhancing the activity of the carboxypeptidase vasohibin/small vasohibin-binding protein.

Asymmetric cell division, which occurs when a mother cell gives rise to two daughter cells with different fates, is crucial for generating diversity during development and for the function of stem cells. Studies in flies and worms have provided important advances for understanding this process.

The centriole exhibits an evolutionarily conserved 9-fold radial symmetry that stems from a cartwheel containing vertically stacked ring polymers that harbor 9 homodimers of the protein SAS-6. Here the authors show how dual properties inherent to surface-guided SAS-6 self-assembly possess spatial information that dictates correct scaffolding of centriole architecture.

The acetyltransferases KAT2A and KAT2B are essential regulators of transcription, cell cycle progression and DNA repair. Here the authors describe a KAT2A/2B-dependent acetylome, and show that acetylation of the protein kinase PLK4 contributes to the regulation of centrosome number.

The centriole is an organelle composed of rings of SAS-6 proteins that form a cartwheel structure. Here the authors develop a cell-free system to examine core cartwheel assembly ofC. reinhardtiiproteins and discover that CrSAS-6 has autonomous properties that facilitates self-organized stacking of pairs of rings.

Centriole biogenesis begins with self-assembly of SAS-6 proteins into 9-fold symmetrical ring polymers, which then stack into a cartwheel that scaffolds organelle formation. Here, the authors develop monobodies against Chlamydomonas reinhardtii SAS-6 and use X-ray crystallography, atomic force microscopy and cryo-electron microscopy to reveal insights into ring assembly and stacking.

Correct spindle positioning is critical for cell division but the full set of proteins regulating this is unclear. Here, with a live imaging siRNA-based screen in human cells, the authors identify 16 candidates required for this process, 11 of which were previously unassociated with such a function, including TYRO3 and GAK.

Microtubule asters are positioned precisely within cells by forces generated by molecular motors, but it is unclear how these are integrated in space and time. Here the authors perform in vivo drag measurements and genetic manipulations to determine the balance of forces that position microtubule asters in C. elegans zygotes.

A computational and analytical framework enables multicolor 3D particle reconstruction of protein complexes from 2D images. The authors demonstrate the power of the approach by reconstructing native proteins within the human centriole.

High-speed photothermal off-resonance AFM is developed, capable of monitoring macromolecular self-assembly driven by weak interactions.

LIN-5 acts at the cortex with Ga to control spindle positioning but is also localized at spindle poles. The LIN-5 interacting protein ASPM-1 and calmodulin are required for its recruitment to spindle poles and the LIN-5/ASPM-1/calmodulin complex regulates meiotic spindle positioning.

The PLK4 kinase and centrosomal protein HsSAS-6 both regulate centrosome duplication. PLK4 negatively controls an FBXW5-containing ubiquitin ligase, which targets SAS-6 for destruction to restrict centrosome re-duplication.

Carrying out high-throughput, cell-based RNA interference screens involves making a range of decisions, from choosing the cell type and reagents to picking strategies for optimization and validation. Informed planning at each stage allows the power of this approach to be maximized.