Mitotic endosomes regulate spindle organization and function via Occludin and FIP5 binding
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ABSTRACT:
PROVIDER: PRJNA1015131 | ENA |
REPOSITORIES: ENA
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Project description:The genetic basis of vertebrate emergence is a major unanswered question in metazoan evolution. Understanding vertebrate-specific genes, such as Occludin (Ocln), may help answer this question. Here, we show that mammary glands lacking Ocln exhibit retarded branching, resulting from reduced cell proliferation. Interestingly, Ocln regulates spindle orientation and function, and its loss leads to a range of phenotypes, including prolonged prophase and failed nuclear and/or cytoplasmic division.
2025-09-11 | GSE242842 | GEO
Project description:Mitotic spindle orientation is crucial for cell fate determination and tissue organization. Although the intracellular machinery governing spindle orientation is well characterized, whether and how secreted factors, such as morphogens, regulate this process remains poorly understood. This study investigated the role of Hedgehog (HH) signaling in modulating mitotic spindle orientation in neural progenitor cells and in induced pluripotent stem cells (iPSCs). Time-lapse microscopy of cerebral organoids and iPSCs revealed that HH signaling increases the angle of the mitotic spindle relative to the apical surface, prolongs mitosis, and enhances spindle rotation. Mechanistically, HH signaling reduces both the number and the length of astral microtubules, key regulators of spindle orientation. This reduction correlates with increased spindle angle in iPSCs. Furthermore, we show that canonical HH signaling, involving GLI-dependent transcriptional regulation, contributes to these effects. RNA sequencing and gene set enrichment analysis (GSEA) revealed that HH signaling upregulates genes associated with microtubule depolymerization, suggesting a transcriptional mechanism by which HH signaling influences astral microtubule dynamics and, consequently, mitotic spindle orientation. These findings highlight a novel link between a morphogen, transcriptional regulation, and the control of mitotic spindle orientation, with implications for development and tissue homeostasis.
2025-06-25 | GSE296672 | GEO
Project description:Animal cells dismantle their nuclear envelope (NE) at the beginning and reconstruct it at the end of mitosis. This process is closely coordinated with spindle pole organization: poles enlarge at mitotic onset and reduce in size as mitosis concludes. The significance of this coordination remains unknown. Here, we demonstrate that Aurora A maintains a pole-localized protein NuMA in a dynamic state during anaphase. Without Aurora A activity, NuMA shifts from a dynamic to a solid state and abnormally accumulates at the poles, causing the segregated chromosome sets to bend around the NuMA-enriched poles. NuMA localization at the poles relies on interactions with dynein/dynactin, its coiled-coil domain, and an intrinsically disordered region (IDR). Mutagenesis experiments revealed that cation- interactions within IDR are key for NuMA pole localization, while glutamine residues trigger the solid-state transition of NuMA upon Aurora A inhibition. We propose that maintaining the proper material properties of the spindle poles is a key step in choreographing accurate organization of the nucleus and genome post-mitosis.
2025-08-09 | GSE277941 | GEO
Project description:During interphase, Rab11-GTPase-containing endosomes recycle endocytic cargo. However, little is known about Rab11 endosomes in mitosis. Here, we show that Rab11 localizes to the mitotic spindle and regulates dynein-dependent endosome localization at poles. We found that mitotic recycling endosomes bind γ-TuRC components and associate with tubulin in vitro. Rab11 depletion or dominant-negative Rab11 expression disrupts astral microtubules, delays mitosis, and redistributes spindle pole proteins. Reciprocally, constitutively active Rab11 increases astral microtubules, restores γ-tubulin spindle pole localization, and generates robust spindles. This suggests a role for Rab11 activity in spindle pole maturation during mitosis. Rab11 depletion causes misorientation of the mitotic spindle and the plane of cell division. These findings suggest a molecular mechanism for the organization of astral microtubules and the mitotic spindle through Rab11-dependent control of spindle pole assembly and function. We propose that Rab11 and its associated endosomes cocontribute to these processes through retrograde transport to poles by dynein.
| S-EPMC4030695 | biostudies-literature
Project description:Aurora A Regulates the Material Property of Spindle Poles to Orchestrate Nuclear Organization at Mitotic Exit
| PRJNA1164781 | ENA
Project description:The concerted action of many protein kinases helps orchestrate the error-free progression through mitosis of mammalian cells. The roles and regulation of some prominent mitotic kinases, such as cyclin-dependent kinases, are well-established. However, these and other known mitotic kinases alone cannot account for the extent of protein phosphorylation that has been reported during mammalian mitosis. Here we demonstrate that CK1α, of the casein kinase 1 family of protein kinases, localises to the spindle and is required for proper spindle-positioning and timely cell division. CK1α is recruited to the spindle by FAM83D, and cells devoid of FAM83D, or those harbouring CK1α-binding-deficient FAM83DF283A/F283A knockin mutation, display pronounced spindle-positioning defects, and a prolonged mitosis. Restoring FAM83D at the endogenous locus in FAM83D-/- cells, or artificially delivering CK1α to the spindle in FAM83DF283A/F283A cells, rescues these defects. These findings implicate CK1α as new mitotic kinase that orchestrates the kinetics and orientation of cell division.
2019-07-15 | PXD013808 | Pride
Project description:We present a snapshot of the regulation of mitotic-spindle proteins and their phosphorylation status in the absence of clathrin during metaphase. A reference list of proteins and phosphosites identified from a mitotic spindle preparation was generated using a label-free and a parallel chemical dimethyl isotopic peptide labelling approach. We further designed experiments to analyse proteins and phosphosites at the mitotic spindle whose abundance was affected by the knock-down of clathrin. We used dimethylation labelling of peptides in combination with fractionation strategies to identify and quantify phosphopeptides enriched by TiO2 beads and the flow-through non-phoshopeptides by ESI-LC-MS/MS for a broad coverage of the mitotic spindle proteome in the absence of clathrin.
2016-05-17 | PXD001603 | Pride
Project description:Sequencial functions of CPEB1 and CPEB4 in the localization of repressed mRNAs to the mitotic spindle and their subsequent phase-specific activation to promote cell phase transitions and correct chromosome segregation
2018-02-15 | GSE100764 | GEO
Project description:Here we show sequential functions of CPEB1 and CPEB4 in the localization of repressed mRNAs to the mitotic spindle and their subsequent phase -specific activation to promote cell phase transitions and correct chromosome segregation.
2021-06-29 | GSE99810 | GEO
Project description:Staufen1 (STAU1) is an RNA-binding protein involved in maturation, localization, translation and decay of mRNAs. STAU1 expression is modulated during the cell cycle and decreases during mitosis. In prometaphase, STAU155 binds specific classes of mRNAs that code for proteins implicated in transcription and cell cycle regulation. In this paper, we report that STAU155 co-localizes with microtubules on the mitotic spindle in human colorectal cancer cell line HCT116, and map the molecular determinant required for this association within the N-terminal 88 amino acids (aa 25-37). Interestingly, STAU1 co-purifies with ribosomal proteins and co-localizes with active sites of translation on the mitotic spindle. To characterize STAU1-dependent mRNA transport and localization on the spindle, we used RNAseq analysis to identify spindle-associated mRNAs on purified spindles of wild-type and STAU1-KO CRISPR cell lines. Our datasets identify 161 protein-coding transcripts that are less abundant on the mitotic spindle of STAU1-KO cells compared to WT, and 660 that are more abundant. Altogether, these data demonstrate that STAU1 controls the transport and the localization of specific sub-populations of mRNAs to the mitotic spindle of cancer cells and suggest that at least some spindle-localized mRNAs undergo local translation during mitosis.
2019-10-05 | GSE138441 | GEO