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Centrosomes, the main microtubule-organizing centers in animal cells, orchestrate cell division and the building of cilia, which carry out a wide array of sensory and motile functions. Here, our Editorial Board Member Tiago Dantas and the in-house editors present a collection of articles published in Communications Biology that highlight the roles of these vital organelles.
Centrosomes are the main microtubule-organizing centers in animal cells, indispensable for cell division and the building of a wide range of cilia, which include sensory and motile cilia. We are now inviting submissions related to the fascinating field of centrosomes, cilia and all of the processes that they are involved in with the aim of highlighting this work in a Special Collection.
Shortly after the onset of ciliogenesis in Caenorhabditis elegans sensory neurons, the centrioles/basal bodies undergo degeneration. The fate of the pericentriolar material (PCM) that was associated with those centrioles has, however, remained unknown. Two recent studies by the Dammermann and the Feldman groups now show that not only does the PCM persist at the ciliary base, it also continues to assemble in the absence of canonical centrioles. Importantly, these neuronal centrosomes retain the ability to function as the cell’s main microtubule-organizing center and support ciliary function.
Cody Aros, Carla Pantoja, and Brigitte Gomperts review the key role of Wnt signaling in all aspects of lung development, repair, and disease progression. They provide an overview of recent research findings and highlight where research is needed to further elucidate mechanisms of action, with the aim of improving disease treatments.
Cilia assembly and function require intraflagellar transport (IFT), a mechanism that uses “trains” to transport cargoes into and out of cilia. While much has been learned about IFT in the past decades, IFT train assembly, loading of cargo and transport regulation have remained poorly understood. In a recent study, Hesketh, Mukhopadhyay and colleagues obtained the complete structure of the IFT-A complex, a key element of IFT trains. By modelling IFT-A into anterograde trains and performing structure-guided mutagenesis, the authors uncover how the IFT-A complex polymerizes and forms carriages to accomplish its distinctive functions.
Uda Ho et al find that loss of centriolar scaffold protein WDR62 in mouse testis leads to defects in spermatogenesis. They find that WDR62 deficiency leads to centriole underduplication in spermatocytes and delayed manchette removal in spermatids due to delayed Katanin p80 accumulation.
Wang et al develop tools to target the mitotic regulator AURKA by synthesising PROTACs based on the inhibitor MLN8237. They find that the new PROTAC compound efficiently clears cytoplasmic and mitotic spindle-associated AURKA but does not eliminate AURKA activity from centrosomes, demonstrating the possibility of targeting subpopulations.
Using experimental data, the authors assess the quality and discuss the limitations of AlphaFold2 predictions of protein structures and protein-protein interactions essential for centrosome and centriole biogenesis.
Rosendo-Pineda et al. discover that N-methyl-D-aspartate receptors (NMDAR) mediate transient calcium entry in mitosis, dependent on phosphorylation of NMDAR by Cyclin B1/CDK1. They also find that phosphorylation-mimicking mutants of NMDAR cause mitotic defects, suggesting that precise control of NMDAR-mediated calcium entry is needed for proper mitosis.
Sinha et al. demonstrate that overexpression of centrosomal protein Cep55 in mice is sufficient to cause a wide-spectrum of cancer via multiple mechanisms including hyperactivation of the Pi3k/Akt pathway, stabilized microtubules and a defective replication checkpoint response. These findings are relevant to human cancers as high CEP55 expression is associated with worse prognosis across multiple cancer types.
Kazazian and colleagues identify FAM46C/TENT5C as an interactor and negative regulator of PLK4 activity in centriole duplication. The authors also find that FAM46C expression strongly reduces cancer cell invasion, uncovering a role for FAM46C as tumor suppressor.
Owa and Dynlacht employ an auxin-inducible degron system to achieve acute degradation of CENP-E. As a result, the authors reveal a kinetochore-independent role for CENP-E that removes PCM1 from centrosomes in interphase, with implications in microcephaly.
Sandhu et al. report that the synaptonemal complex (SC) protein, TEX12, localises to centrosomes independently of the SC during meiosis. They also show that it provokes centrosome amplification in somatic cells, a pathology associated with cancer development.
The X-ray crystal structures of C-terminal mutants of the coiled-coil protein cancer testis antigen TEX12 in combination with modeling of the TEX12 wild-type dimer reveal the protein’s control of its oligomeric state, which resembles assembly of its complex with synaptonemal complex central element protein SYCE2.
Dang Ngoc Anh Suong et al find that vertical mixing generates iPSC-derived brain organoids displaying an inverted structure with neurons localising at the centre and neural progenitors at the outside. This study illustrates the influence of fluid mechanics relevant to the direction of primary cilia on stem cell differentiation.
Petsouki et al. dissect the importance of FBW7-mediated regulation of NDE1 and TALPID3 in mesenchymal stem cells (MSCs). They find that by modulating the abundance of negative (NDE1) and positive (TALPID3) cilia regulators, FBW7 contributes to both the assembly and signaling functions of primary cilia that are necessary for osteoblast differentiation.
Park et al. characterise the interactome, localisation and function of Actin-Related Protein-Testis1 protein (ARP-T1), encoded by the ACTRT1 gene, associated with inherited basal cell cancer. They find that ARP-T1 is localised to the primary cilia basal body in epidermal cells, interacts with the cilia machinery, and is needed for proper ciliogenesis.
Lori Peacock et al. report the sequence of meiosis in Trypanosoma brucei cells from the salivary glands of tsetse flies using image analyses and expression of the cell fusion protein HAP2. From the recovered cell types and expression of HAP2 in meiotic intermediates, these results indicate that haploid gametes are produced sequentially.
Laruelle et al. present a fitting based computational method called SET that can detect hidden spatial structure in cell tissue organization in a statistically significant manner using a single image and without any parameter settings. They exemplify the utility of the approach by identifying invisible cell and subcellular patterns.
Lars Maerz et al. show that pharmacological inhibition of cholesterol synthesis in zebrafish embryos leads to organ malformations and dysfunctions in cilium formation and signaling. These findings together with alterations to the cilia transition zone suggest an important role of cholesterol in cilia biogenesis and function.
By using methods to synthesise or degrade PIP2 selectively in the ciliary membrane, Stilling et al. find that PIP2 levels determine the length of primary cilia. They show that various pathways converge on PIP2 which induces ciliary fission in a manner dependent on actin, AurkA and HDAC6.
Lim et al. find that osteoblast-specific deletion of IFT20 impairs osteoblast/osteocyte cell alignment and reduces bone mass. Their results further show that the mechanism underlying IFT20-associated bone ciliopathies involves defects in cell polarity caused by deficient Ceramide-PKCζ recruitment to cilia and reduced β-catenin signaling, which interferes with bone development.
Marumo and colleagues use three-dimensional tracking of fluorescent microbeads to visualize the helical swimming of the cilliate Tetrahymena. They reveal that the beating pattern of the cilia determines the swimming behavior.
Lauren Malave et al. examine the impact of sonic hedgehog signaling in the dorsal striatum in L-Dopa induced dyskinesia (LID) animal models. Their results suggest that increasing sonic hedgehog signaling can reduce the severity of LID and abnormal involuntary movements, suggesting future therapeutic approaches to mitigate dyskinetic comorbidities of long-term treatment with L-Dopa.
Reilly et al identify a neuropeptide-neuropeptide receptor (NP/NPR) module that is active in male but not in hermaphrodite C. elegans. Using a neuropeptide rescue paradigm, they demonstrate that receptor expression within pre-motor neurons mediates coordination of male-specific and core locomotor circuitries.
Cheryl L Ames, Anna Klompen et al. describe cassiosomes, stinging cell structures in the mucus of the upside-down jellyfish Cassiopea xamachana. They show that these motile cell masses consist of an outer epithelial layer largely composed of nematocytes surrounding centralized clusters of endosymbiotic dinoflagellates.
Keita Sasaki, Kogiku Shiba, Akihiro Nakamura et al. show that mice lacking calaxin have intact fertility despite showing primary cilia dyskinesia and abnormal 9 + 0 nodal cilia formation, while loss of calaxin in zebrafish causes situs inversus but does not affect 9 + 2 axonemal formation. Together, these findings suggest a specific role for calaxin in 9 + 0 nodal cilia development.
Yoshinori Abe et al. find that the Hedgehog (HH) signalling effector GLI1 is methylated by and associates with the MEP50/PRMT5 methyltransferase complex upon HH activation. They find that this complex plays a key role in positive feedback regulation of HH signalling in cancer.
Verschueren et al. expand our understanding of the Stiles-Crawford effect in mammals by using super-high resolution expansion microscopy of the adult macaque eye. They show that cone photoreceptors have a planar polarity organized radially around the optical center of the eye and that Usher proteins establish a mechanical continuity between the outer and inner segments, which sheds light on the Stiles-Crawford effect in this species.
Single-molecule tracking of the sensory transmembrane protein OCR-2 in C. elegans reveals an interplay of transport modes during intraflagellar transport in the cilium.