Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna

Rocha, Cecilia; Prinos, Panagiotis

doi:10.3389/fncel.2022.809917

Cited by 7 publications

(10 citation statements)

References 144 publications

(172 reference statements)

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“…Similarly, mRNAs that are no longer needed can be readily shuttled away in a translationally-suppressed condition until they are required again, or destroyed. P-bodies, cytoplasmic entities that participate in mRNA processing and degradation and share components with stress granules, appear to co-localize with centrosomes (Aizer & Shav-Tal, 2008) or ciliary basal bodies (Rocha & Prinos, 2022). Notably, P-bodies have also been found to include centriolar satellite proteins such as CEP192, OFD1, PCM1, and CEP131.…”

Section: Delivering the Message: Rna And Translation At Centrosomesmentioning

confidence: 99%

New insights into the centrosome‐associated spliceosome components as regulators of ciliogenesis and tissue identity

et al. 2023

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Biomolecular condensates are membrane-less assemblies of proteins and nucleic acids. Centrosomes are biomolecular condensates that play a crucial role in nuclear division, cytoskeletal remodeling, and cilia formation in animal cells. Spatial omics technology is providing new insights into the dynamic exchange of spliceosome components between the nucleus and the centrosome/cilium. Intriguingly, centrosomes are emerging as cytoplasmic sites for information storage, enriched with RNA molecules and RNA-processing proteins. Furthermore, growing evidence supports the view that nuclear spliceosome components assembled at the centrosome function as potential coordinators of splicing subprograms, pluripotency, and cell differentiation.In this article, we first discuss the current understanding of the centrosome/cilium complex, which controls both stem cell differentiation and pluripotency. We next explore the molecular mechanisms that govern splicing factor assembly and disassembly around the centrosome and examine how RNA processing pathways contribute to ciliogenesis. Finally, we discuss numerous unresolved compelling questions regarding the centrosomeassociated spliceosome components and transcript variants within the cytoplasm as sources of RNA-based secondary messages in the regulation of cell identity and cell fate determination.

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Section: Delivering the Message: Rna And Translation At Centrosomesmentioning

confidence: 99%

New insights into the centrosome‐associated spliceosome components as regulators of ciliogenesis and tissue identity

et al. 2023

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“…Future studies could investigate the molecular mechanisms behind how OGN levels regulate cilia length, and whether primary cilia transduce different signals at different stages of differentiation. Interestingly, the primary cilium may also facilitate cell-cell communication functions in addition to its role as signal hub to transduce signals [63,67]. Our immunostaining results showed that neuronal cilia form clusters (Figure 2C, Day 55), which possibly allows for cell-cell communication.…”

Section: Discussionmentioning

confidence: 91%

“…In addition to their importance on differentiated neurons, primary cilia also play crucial roles during brain development through the transduction of important signaling pathways, such as Wnt and Shh signaling [63]. Primary cilia are required for the differentiation of neural progenitors and neural stems cells into multiple types of brain cells [64,65].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Primary Cilia Length by O-GlcNAc during Neuronal Development in Human Neuron Model

Tian¹,

Huang²,

Eslami³

et al. 2023

Preprint

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The primary cilium plays critical roles in homeostasis and development of neurons. Recent studies demonstrate that cilia length is regulated by the metabolic state of cells, as dictated by processes such as glucose flux and O-GlcNAcylation (OGN). The study of cilia length regulation during neuron development, however, has been an area left largely unexplored. This project aims to elucidate the roles of O-GlcNAc in neuronal development through its regulation of the primary cilium. Here, we present findings suggesting that OGN levels negatively regulate cilia length on differentiated cortical neurons derived from human-induced pluripotent stem cells. In neurons, cilia length increased significantly during neurons maturation (after day 35), while OGN levels began to drop. Long-term perturbation of OGN via drugs, which inhibit or promote its cycling, during neuron development also have varying effects. Diminishing OGN levels increases cilia length until day 25, when neural stem cells expand and undergo early neurogenesis, before causing cell cycle exit defects and multinucleation. Elevating OGN levels induces greater primary cilia assembly but ultimately results in the development of premature neurons, which have higher insulin sensitivity. These results indicate that OGN levels and primary cilia length are jointly critical in proper neuron development and function. Understanding the interplays between these two nutrient sensors, O-GlcNAc and the primary cilium, during neuron development is important in paving connections between dysfunctional nutrient-sensing and early neurological disorders.

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“…Resembling the noncanonical initiation of the Notch pathway, the later activation of Hh signaling can be categorized into three kinds [40]. Nevertheless, contrary to Notch and other embryonic signaling pathways, the Hh signaling pathway is extremely dependent on the primary cilium [43], a single organelle, with the composition of vital signaling components varying in distribution across the cilium depending on whether Hh signaling is switched on or off [44][45][46].…”

Section: Introductionmentioning

confidence: 99%

The role of Hedgehog and Notch signaling pathway in cancer

Xia

Yang

et al. 2022

Mol Biomed

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Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.

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Post-transcriptional and Post-translational Modifications of Primary Cilia: How to Fine Tune Your Neuronal Antenna

Cited by 7 publications

References 144 publications

New insights into the centrosome‐associated spliceosome components as regulators of ciliogenesis and tissue identity

New insights into the centrosome‐associated spliceosome components as regulators of ciliogenesis and tissue identity

Regulation of Primary Cilia Length by O-GlcNAc during Neuronal Development in Human Neuron Model

The role of Hedgehog and Notch signaling pathway in cancer

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