RAB19 Directs Cortical Remodeling and Membrane Growth for Primary Ciliogenesis

Jewett, Cayla E.; Soh, Adam W. J.; Lin, Carrie H; Lu, Qiumin; Lencer, Ezra; Westlake, Christopher J.; Pearson, Chad G.; Prekeris, Rytis

doi:10.1016/j.devcel.2020.12.003

Cited by 26 publications

(73 citation statements)

References 61 publications

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“…Another intriguing hypothesis is that CPLANE is involved in autophagy since PI(3)P synthesis is critical for autophagy initiation ( 54 ); moreover, autophagic removal of the centriolar satellite pool of OFD1 is required for ciliogenesis ( 55 ) and mutations in CPLANE proteins have been associated with OFD syndromes ( 19 , 56 ). It will also be interesting to determine whether the CPLANE complex impinges on cortical actin clearance, an event that is required for cilium emergence ( 57 ). Last, Intu and Fuz were recently identified as the GEF of Rab23 ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Structure of the ciliogenesis-associated CPLANE complex

et al. 2022

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Dysfunctional cilia cause pleiotropic human diseases termed ciliopathies. These hereditary maladies are often caused by defects in cilia assembly, a complex event that is regulated by the ciliogenesis and planar polarity effector (CPLANE) proteins Wdpcp, Inturned, and Fuzzy. CPLANE proteins are essential for building the cilium and are mutated in multiple ciliopathies, yet their structure and molecular functions remain elusive. Here, we show that mammalian CPLANE proteins comprise a bona fide complex and report the near-atomic resolution structures of the human Wdpcp-Inturned-Fuzzy complex and of the mouse Wdpcp-Inturned-Fuzzy complex bound to the small guanosine triphosphatase Rsg1. Notably, the crescent-shaped CPLANE complex binds phospholipids such as phosphatidylinositol 3-phosphate via multiple modules and a CPLANE ciliopathy mutant exhibits aberrant lipid binding. Our study provides critical structural and functional insights into an enigmatic ciliogenesis-associated complex as well as unexpected molecular rationales for ciliopathies.

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Section: Discussionmentioning

confidence: 99%

Structure of the ciliogenesis-associated CPLANE complex

et al. 2022

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“…Centriole migration to the apical surface requires actomyosin contractility and microtubule network remodeling (Hong et al, 2015;Pitaval et al, 2017). Actin is also cleared from the site of apical docking (Francis et al, 2011;Jewett et al, 2021), and a recent study (Insinna et al, 2019) identified a membrane channel connecting the ciliary vesicle to the plasma membrane during ciliogenesis that may guide the centriole to the apical membrane.…”

Section: Introductionmentioning

confidence: 99%

Hedgehog signaling and the primary cilium: implications for spatial and temporal constraints on signaling

Stearns

2021

Development

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The mechanisms of vertebrate Hedgehog signaling are linked to the biology of the primary cilium, an antenna-like organelle that projects from the surface of most vertebrate cell types. Although the advantages of restricting signal transduction to cilia are often noted, the constraints imposed are less frequently considered, and yet they are central to how Hedgehog signaling operates in developing tissues. In this Review, we synthesize current understanding of Hedgehog signal transduction, ligand secretion and transport, and cilia dynamics to explore the temporal and spatial constraints imposed by the primary cilium on Hedgehog signaling in vivo.

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“…The current research on RAB19 is not very clear. Some studies have reported that in colorectal cancer, RABs may play an important role in regulating cell cycle and immune-related pathways, and in gastric cancer, the miR495-5p/RAB19 axis inhibits its proliferation, migration, and invasion, so RAB19 perhaps be a potential biomarker for predicting the prognosis and immunotherapeutic response of related tumors ( Hu and Ji, 2021 ; Jewett et al, 2021 ; Jiang et al, 2022 ). GOPC, a protein that containing a coiled helix motif, is also one of the prognostic markers of Early-Stage Lung Squamous Cell Carcinoma, and when fused with ROS1 and other ROS1, it can represent a rare but recurrent drug target in various glioma types ( Li et al, 2021 ; Sievers et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma

Luo

Zhang

et al. 2022

Front. Cell Dev. Biol.

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N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approach for tumor treatment. However, as far as the stomach adenocarcinoma (STAD) is concerned, the in-depth research is still a gap in the m6A-associated immune markers. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases is extremely important for our research, where we obtained gene mutation, gene expression data and relevant clinical information of STAD patients. Firstly, the samples from GEO were used as external validation groups, while the TCGA samples were divided into a training group and an internal validation group randomly. Using the way of Single factor COX-LASSO- and multi-factor Cox to construct the prognostic model. Then, all samples were subjected to cluster analysis to generate high and low expression groups of immune gene. Meanwhile, we also collected the correlation between these types and tumor microenvironment. On this basis, a web version of the dynamic nomogram APP was developed. In addition, we performed microenvironmental correlation, copy number variation and mutation analyses for model genes. The prognostic model for STAD developed here demonstrated a very strong predictive ability. The results of cluster analysis manifested that the immune gene low expression group had lower survival rate and higher degree of immune infiltration. Therefore, the immune gene low expression group was associated with lower survival rates and a higher degree of immune infiltration. Gene set enrichment analysis suggested that the potential mechanism might be related to the activation of immunosuppressive functions and multiple signaling pathways. Correspondingly, the web version of the dynamic nomogram APP produced by the DynNom package has successfully achieved rapid and accurate calculation of patient survival rates. Finally, the multi-omics analysis of model genes further enriched the research content. Interference of RAB19 was confirmed to facilitate migration of STAD cells in vitro, while its overexpression inhibited these features. The prognostic model for STAD constructed in this study is accurate and efficient based on multi-omics analysis and experimental validation. Additionally, the results of the correlation analysis between the tumor microenvironment and m6Ascore are the basics of further exploration of the pathophysiological mechanism in STAD.

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RAB19 Directs Cortical Remodeling and Membrane Growth for Primary Ciliogenesis

Cited by 26 publications

References 61 publications

Structure of the ciliogenesis-associated CPLANE complex

Structure of the ciliogenesis-associated CPLANE complex

Hedgehog signaling and the primary cilium: implications for spatial and temporal constraints on signaling

Prognostic Role of M6A-Associated Immune Genes and Cluster-Related Tumor Microenvironment Analysis: A Multi-Omics Practice in Stomach Adenocarcinoma

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