Small GTPases最新文献_第5页

Rab22a regulates the establishment of epithelial polarity. Rab22a调控上皮极性的建立。

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-04-17 DOI: 10.1080/21541248.2020.1754104

Isabella R Blum, Caroline Behling-Hess, Marco Padilla-Rodriguez, Samina Momtaz, Christopher Cox, Jean M Wilson

{"title":"Rab22a regulates the establishment of epithelial polarity.","authors":"Isabella R Blum, Caroline Behling-Hess, Marco Padilla-Rodriguez, Samina Momtaz, Christopher Cox, Jean M Wilson","doi":"10.1080/21541248.2020.1754104","DOIUrl":"https://doi.org/10.1080/21541248.2020.1754104","url":null,"abstract":"Membrane trafficking establishes and maintains epithelial polarity. Rab22a has a polarized distribution in activated T-cells, but its role in epithelial polarity has not been investigated. We showed previously that Rab14 acts upstream of Arf6 to establish the apical membrane initiation site (AMIS), but its interaction with Rab22a is unknown. Here we show that Rab14 and Rab22a colocalize in endosomes of both unpolarized and polarized MDCK cells and Rab22a localizes to the cell:cell interface of polarizing cell pairs. Knockdown of Rab22a results in a multi-lumen phenotype in three-dimensional culture. Further, overexpression of Rab22a in Rab14 knockdown cells rescues the multi-lumen phenotype observed with Rab14 knockdown, suggesting that Rab22a is downstream of Rab14. Because of the relationship between Rab14 and Arf6, we investigated the effect of Rab22a knockdown on Arf6. We find that Rab22a knockdown results in decreased active Arf6 and that Rab22a co-immunoprecipitates with the Arf6 GEF EFA6. In addition, EFA6 is retained in intracellular puncta in Rab22a KD cells. These results suggest that Rab22a acts downstream of Rab14 to traffic EFA6 to the AMIS to regulate Arf6 in the establishment of polarity.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"12 4","pages":"282-293"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2020.1754104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37828019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

A regulatory role of membrane by direct modulation of the catalytic kinase domain. 膜通过直接调节催化激酶结构域的调节作用。

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-07-14 DOI: 10.1080/21541248.2020.1788886

Priyanka Prakash

引用次数: 2

Selection of established tumour cells through narrow diameter micropores enriches for elevated Ras/Raf/MEK/ERK MAPK signalling and enhanced tumour growth. 通过窄直径微孔选择已确定的肿瘤细胞，可富集升高的 Ras/Raf/MEK/ERK MAPK 信号并促进肿瘤生长。

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-06-22 DOI: 10.1080/21541248.2020.1780108

Dominika A Rudzka, Susan Mason, Matthew Neilson, Lynn McGarry, Gabriela Kalna, Ann Hedley, Karen Blyth, Michael F Olson

{"title":"Selection of established tumour cells through narrow diameter micropores enriches for elevated Ras/Raf/MEK/ERK MAPK signalling and enhanced tumour growth.","authors":"Dominika A Rudzka, Susan Mason, Matthew Neilson, Lynn McGarry, Gabriela Kalna, Ann Hedley, Karen Blyth, Michael F Olson","doi":"10.1080/21541248.2020.1780108","DOIUrl":"10.1080/21541248.2020.1780108","url":null,"abstract":"As normal cells become cancer cells, and progress towards malignancy, they become progressively softer. Advantages of this change are that tumour cells become more deformable, and better able to move through narrow constraints. We designed a positive selection strategy that enriched for cells which could move through narrow diameter micropores to identify cell phenotypes that enabled constrained migration. Using human MDA MB 231 breast cancer and MDA MB 435 melanoma cancer cells, we found that micropore selection favoured cells with relatively higher Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signalling, which affected actin cytoskeleton organization, focal adhesion density and cell elasticity. In this follow-up study, we provide further evidence that selection through micropores enriched for cells with altered cell morphology and adhesion. Additional analysis of RNA sequencing data revealed a set of transcripts associated with small cell size that was independent of constrained migration. Gene set enrichment analysis identified the 'matrisome' as the most significantly altered gene set linked with small size. When grown as orthotopic xenograft tumours in immunocompromised mice, micropore selected cells grew significantly faster than Parent or Flow-Sorted cells. Using mathematical modelling, we determined that there is an interaction between 1) the cell to gap size ratio; 2) the bending rigidity of the cell, which enable movement through narrow gaps. These results extend our previous conclusion that Ras/Raf/MEK/ERK MAPK signalling has a significant role in regulating cell biomechanics by showing that the selective pressure of movement through narrow gaps also enriches for increased tumour growth in vivo.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"12 4","pages":"294-310"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38072849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesis. RhoJ和Cdc42之间的功能性拮抗调节血管生成过程中的纤维连接蛋白重构。

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-08-28 DOI: 10.1080/21541248.2020.1809927

Ananthalakshmy Sundararaman, Harry Mellor

{"title":"A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesis.","authors":"Ananthalakshmy Sundararaman, Harry Mellor","doi":"10.1080/21541248.2020.1809927","DOIUrl":"https://doi.org/10.1080/21541248.2020.1809927","url":null,"abstract":"Angiogenesis is the formation of new blood vessels from pre-existing ones. Angiogenesis requires endothelial cells to change shape and polarity, as well as acquire the ability to directionally migrate ‒ processes that are classically regulated by the Rho family of GTPases. RhoJ (previously TCL) is an endothelium enriched Rho GTPase with a 78% amino acid similarity to the ubiquitously expressed Cdc42. In our recent publication, we demonstrate that α5β1 integrin co-traffics with RhoJ. RhoJ specifically represses the internalization of the active α5β1 conformer, leading to a reduced ability of endothelial cells to form fibronectin fibrils. Surprisingly, this function of RhoJ is in opposition to the role of Cdc42, a known driver of fibrillogenesis. Intriguingly, we discovered that the competition for limiting amounts of the shared effector, PAK3, could explain the ability of these two Rho GTPases to regulate fibrillogenesis in opposing directions. Consequently, RhoJ null mice show excessive fibronectin deposition around retinal vessels, possibly due to the unopposed action of Cdc42. Our work suggests that the functional antagonism between RhoJ and Cdc42 could restrict fibronectin remodelling to sites of active angiogenesis to form a provisional matrix for vessel growth. One correlate of our findings is that RhoJ dependent repression of fibronectin remodelling could be atheroprotective in quiescent vessels.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"12 4","pages":"241-245"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2020.1809927","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38319893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Targeting effector pathways in RAC1^P29S-driven malignant melanoma. rac1p29s驱动的恶性黑色素瘤靶向效应通路

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-02-17 DOI: 10.1080/21541248.2020.1728469

Cristina Uribe-Alvarez, Sandra Lucía Guerrero-Rodríguez, Jennifer Rhodes, Alexa Cannon, Jonathan Chernoff, Daniela Araiza-Olivera

{"title":"Targeting effector pathways in RAC1P29S-driven malignant melanoma.","authors":"Cristina Uribe-Alvarez, Sandra Lucía Guerrero-Rodríguez, Jennifer Rhodes, Alexa Cannon, Jonathan Chernoff, Daniela Araiza-Olivera","doi":"10.1080/21541248.2020.1728469","DOIUrl":"https://doi.org/10.1080/21541248.2020.1728469","url":null,"abstract":"Malignant melanoma is characterized by mutations in a number of driver genes, most notably BRAF and NRAS. Recent genomic analyses revealed that 4-9% of sun-exposed melanomas bear activating mutations in RAC1, which encodes a small GTPase that is known to play key roles in cell proliferation, survival, and migration. The RAC1 protein activates several effector pathways, including Group A p21-activated kinases (PAKs), phosphoinositol-3-kinases (PI3Ks), in particular the beta isoform, and the serum-response factor/myocardin-related transcription factor (SRF/MRTF). Having previously shown that inhibition of Group A PAKs impedes oncogenic signalling from RAC1P29S, we here extend this analysis to examine the roles of PI3Ks and SRF/MRTF in melanocytes and/or in a zebrafish model. We demonstrate that a selective Group A PAK inhibitor (Frax-1036), a pan-PI3K (BKM120), and two PI3Kβ inhibitors (TGX221, GSK2636771) impede the growth of melanoma cells driven by mutant RAC1 but not by mutant BRAF, while other PI3K selective inhibitors, including PI3Kα, δ and γ, are less effective. Using these compounds as well as an SRF/MRTF inhibitor (CCG-203,971), we observed similar results in vivo, using embryonic zebrafish development as a readout. These results suggest that targeting Group A PAKs, PI3Kβ, and/or SRF/MRTF represent a promising approach to suppress RAC1 signalling in malignant melanoma.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"12 4","pages":"273-281"},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2020.1728469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37630749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Cdc42 promotes Bgs1 recruitment for septum synthesis and glucanase localization for cell separation during cytokinesis in fission yeast. 在分裂酵母细胞分裂过程中，Cdc42促进Bgs1募集用于隔膜合成和葡聚糖酶定位用于细胞分离。

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-03-22 DOI: 10.1080/21541248.2020.1743926

Udo N Onwubiko, Julie Rich-Robinson, Rose Albu Mustaf, Maitreyi E Das

引用次数: 6

Exploring a role for fatty acid synthase in prostate cancer cell migration. 探讨脂肪酸合酶在前列腺癌细胞迁移中的作用。

Small GTPases Pub Date : 2021-07-01 Epub Date: 2020-10-12 DOI: 10.1080/21541248.2020.1826781

Mario De Piano, Valeria Manuelli, Giorgia Zadra, Massimo Loda, Gordon Muir, Ash Chandra, Jonathan Morris, Mieke Van Hemelrijck, Claire M Wells

引用次数: 6

Complementary functions for the Ran gradient during division. 除法时Ran梯度的互补函数。

Small GTPases Pub Date : 2021-05-01 Epub Date: 2020-02-14 DOI: 10.1080/21541248.2020.1725371

Imge Ozugergin, Alisa Piekny

引用次数: 12

Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context. 大肠和结直肠癌背景下ras -效应物相互作用竞争分析。

Small GTPases Pub Date : 2021-05-01 Epub Date: 2020-02-14 DOI: 10.1080/21541248.2020.1724596

Verónica Ibáňez Gaspar, Simona Catozzi, Camille Ternet, Philip J Luthert, Christina Kiel

{"title":"Analysis of Ras-effector interaction competition in large intestine and colorectal cancer context.","authors":"Verónica Ibáňez Gaspar, Simona Catozzi, Camille Ternet, Philip J Luthert, Christina Kiel","doi":"10.1080/21541248.2020.1724596","DOIUrl":"https://doi.org/10.1080/21541248.2020.1724596","url":null,"abstract":"Cancer is the second leading cause of death globally, and colorectal cancer (CRC) is among the five most common cancers. The small GTPase KRAS is an oncogene that is mutated in ~30% of all CRCs. Pharmacological treatments of CRC are currently unsatisfactory, but much hope rests on network-centric approaches to drug development and cancer treatment. These approaches, however, require a better understanding of how networks downstream of Ras oncoproteins are connected in a particular tissue context - here colon and CRC. Previously we have shown that competition for binding to a 'hub' protein, such as Ras, can induce a rewiring of signal transduction networks. In this study, we analysed 56 established and predicted effectors that contain a structural domain with the potential ability to bind to Ras oncoproteins and their link to pathways coordinating intestinal homoeostasis and barrier function. Using protein concentrations in colon tissue and Ras-effector binding affinities, a computational network model was generated that predicted how effectors differentially and competitively bind to Ras in colon context. The model also predicted both qualitative and quantitative changes in Ras-effector complex formations with increased levels of active Ras - to simulate its upregulation in cancer - simply as an emergent property of competition for the same binding interface on the surface of Ras. We also considered how the number of Ras-effector complexes at the membrane can be increased by additional domains present in some effectors that are recruited to the membrane in response to specific conditions (inputs/stimuli/growth factors) in colon context and CRC.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":"12 3","pages":"209-225"},"PeriodicalIF":0.0,"publicationDate":"2021-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2020.1724596","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37643062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 15

ARL3, a small GTPase with a functionally conserved role in primary cilia and immune synapses. ARL3，一个小的GTPase，在初级纤毛和免疫突触中具有功能保守的作用。

Small GTPases Pub Date : 2021-05-01 Epub Date: 2019-12-18 DOI: 10.1080/21541248.2019.1703466

Laura Powell, Youhani H Samarakoon, Shehab Ismail, John A Sayer

引用次数: 0