Rap1gap2 regulates axon outgrowth in olfactory sensory neurons

Sadrian, Benjamin; Cheng, Ting Wen; Shull, Olivia; Gong, Qizhi

doi:10.1016/j.mcn.2012.06.003

Cited by 3 publications

(3 citation statements)

References 76 publications

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“…To specifically determine the consequences of satellite loss on the cellular abundance of centrosome proteins, we cross‐correlated the global proteome dataset with the published centrosome proteome . Unexpectedly, we found that majority of the 116 centrosome proteome identified remains in place, where only a few proteins including the satellite protein Cep131 and regulatory proteins Ran1Gap2 and Prkar2B were perturbed in the global proteome (Fig B–D) . Consistent with the proteomics data, a significant increase in the cellular abundance of Cep131 and a significant decrease in SLAIN2 was detected using immunoblotting experiments (Fig G).…”

Section: Resultssupporting

confidence: 74%

“…Results shown are the mean of two independent experiments AE SD (100 cells/experiment, *P < 0.5, **P < 0.01, ***P < 0.001, ns: not significant t-test). proteins Ran1Gap2 and Prkar2B were perturbed in the global proteome ( Fig 8B-D) [34,[58][59][60]. Consistent with the proteomics data, a significant increase in the cellular abundance of Cep131 and a significant decrease in SLAIN2 was detected using immunoblotting experiments ( Fig 4G).…”

Section: Loss Of Satellites Leads To a Rearrangement Of The Global Prsupporting

confidence: 83%

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Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action remain poorly understood. Here, we generated a kidney epithelial cell line ( IMCD 3) lacking satellites by CRISPR /Cas9‐mediated PCM 1 deletion and investigated the cellular and molecular consequences of satellite loss. Cells lacking satellites still formed full‐length cilia but at significantly lower numbers, with changes in the centrosomal and cellular levels of key ciliogenesis factors. Using these cells, we identified new ciliary functions of satellites such as regulation of ciliary content, Hedgehog signaling, and epithelial cell organization in three‐dimensional cultures. However, other functions of satellites, namely proliferation, cell cycle progression, and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites affects transcription scarcely, but significantly alters the proteome. Importantly, the centrosome proteome mostly remains unaltered in the cells lacking satellites. Together, our findings identify centriolar satellites as regulators of efficient cilium assembly and function and provide insight into disease mechanisms of ciliopathies.

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Section: Resultssupporting

confidence: 74%

Section: Loss Of Satellites Leads To a Rearrangement Of The Global Prsupporting

confidence: 83%

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

et al. 2019

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“…8C)! (Sadrian et al, 2012;Sha et al, 2018;Sha et al, 2017;Staples et al, 2012). To investigate whether RPE1 PCM1 KO cells had similar changes, we determined the global proteome of these cells using SILAC-based mass spectrometry analysis.…”

Section: Loss Of Satellites Leads To a Rearrangement Of The Global Prmentioning

confidence: 99%

Differential requirement for centriolar satellites in cilium formation among different vertebrate cells

Odabasi

Ohlsen

Gül

et al. 2018

Preprint

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Centriolar satellites are ubiquitous in vertebrate cells. They have recently emerged as key regulators of centrosome/cilium biogenesis, and their mutations are linked to ciliopathies. However, their precise functions and mechanisms of action, which potentially differ between cell types, remain poorly understood.Here, we generated retinal pigmental and kidney epithelial cells lacking satellites by genetically ablating PCM1 to investigate their functions. While satellites were essential for cilium assembly in retinal epithelial cells, kidney epithelial cells lacking satellites still formed full-length cilia but at significantly lower levels, with reduced centrosomal levels of key ciliogenesis factors. Using these cells, we identified the first satellite-specific functions at cilia, specifically in regulating ciliary content, Hedgehog signalling, and epithelial cell organization. However, other satellite-linked functions, namely proliferation, cell cycle progression and centriole duplication, were unaffected in these cells. Quantitative transcriptomic and proteomic profiling revealed that loss of satellites scarcely affects transcription, but significantly alters the proteome, particularly actin cytoskeleton pathways and neuronal functions. Together, our findings identify cell type-specific roles for satellites and provide insight into the phenotypic heterogeneity of ciliopathies.

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Gut microbiota-derived 5-hydroxyindoleacetic acid from Pumpkin Polysaccharides supplementation alleviates colitis through Epac/Rap1 signaling activation

Zhang

Wang

et al. 2023

Preprint

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Aims Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PP) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study explores the potential modulatory roles of gut microbial metabolites (5-hydroxyindole acetic acid, 5-HIAA) after PP treatment in protecting against UC and to elucidate the underlying molecular mechanisms. Results The average molecular weight of PP was 3.10 × 105 Da, and PP mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate (DSS) induced UC on C57BL/6 mice by improving gut microbiota dysbiosis and intestinal mucosal barrier function. Metabolomic profiling analysis showed that PP supplementation resulted in the enrichment of 5-HIAA, which exhibited individual and synergistic anti-UC activities. The results of the transcriptome and confirmatory experiments suggested that Rap1 pathway activation may participate in the anti-UC effect of PPs. 8-pCPT-2’-O-Me-cAMP (Epac/Rap1 signaling antagonist) showed similar anti-UC activity to PP and 5-HIAA, while the effect of ESI-05 (Epac/Rap1 signaling inhibitor) was opposite. Furthermore, exogenous treatment with 5-HIAA activated the Epac/Rap1 signaling pathway both in vitro and in vivo, which may be related to elevated cAMP levels in the colon. Conclusions This study revealed that PP could be developed to treat UC and other diseases associated with an imbalance in the intestinal microbiota. The gut microbiota-5-HIAA-Epac/Rap1 axis plays an important role in intestinal homeostasis and may provide a novel approach for the prevention of UC by manipulating gut microbial serotonin metabolites.

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Rap1gap2 regulates axon outgrowth in olfactory sensory neurons

Cited by 3 publications

References 76 publications

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Centriolar satellites are required for efficient ciliogenesis and ciliary content regulation

Differential requirement for centriolar satellites in cilium formation among different vertebrate cells

Gut microbiota-derived 5-hydroxyindoleacetic acid from Pumpkin Polysaccharides supplementation alleviates colitis through Epac/Rap1 signaling activation

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