Small GTPases最新文献

To stay in shape and keep moving: MLL emerges as a new transcriptional regulator of Rho GTPases. 保持形状并保持运动：MLL作为Rho GTP酶的新转录调节因子出现。

Small GTPases Pub Date : 2023-12-01 DOI: 10.1080/21541248.2023.2254437

Akash Chinchole, Shreyta Gupta, Shweta Tyagi

引用次数: 0

An ultra-sensitive method to detect mutations in human RAS templates 一种检测人类RAS模板突变的超灵敏方法

Small GTPases Pub Date : 2022-06-06 DOI: 10.1080/21541248.2022.2083895

Siqi Li, C. Counter

{"title":"An ultra-sensitive method to detect mutations in human RAS templates","authors":"Siqi Li, C. Counter","doi":"10.1080/21541248.2022.2083895","DOIUrl":"https://doi.org/10.1080/21541248.2022.2083895","url":null,"abstract":"ABSTRACT The RAS family of small GTPases is mutated in roughly a fifth of human cancers. Hotspot point mutations at codons G12, G13, and Q61 account for 95% of all these mutations, which are well established to render the encoded proteins oncogenic. In humans, this family comprises three genes: HRAS, NRAS, and KRAS. Accumulating evidence argues that oncogenic RAS point mutations may be initiating, as they are often truncal in human tumours and capable of inducing tumorigenesis in mice. As such, there is great interest in detecting oncogenic mutation in the RAS genes to understand the origins of cancer, as well as for early detection purposes. To this end, we previously adapted the microbial ultra-sensitive M aximum D epth S equencing (MDS) assay for the murine Kras gene, which was capable of detecting oncogenic mutations in the tissues of mice days after carcinogen exposure, essentially capturing the very first step in tumour initiation. Given this, we report here the adaption and details of this assay to detect mutations in a human KRAS sequence at an analytic sensitivity of one mutation in a million independently barcoded templates. This humanized version of MDS can thus be exploited to detect oncogenic mutations in KRAS at an incredible sensitivity and modified for the same purpose for the other RAS genes.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42208867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A New Crosslinking Assay to Study Guanine Nucleotide Binding in the Gtr Heterodimer of S. cerevisiae. 一种新的研究酿酒葡萄球菌Gtr异源二聚体鸟嘌呤核苷酸结合的交联试验。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2022.2141019

Dylan D Doxsey, Kristen Veinotte, Kuang Shen

引用次数: 1

The progress in C9orf72 research: ALS/FTD pathogenesis, functions and structure. C9orf72的研究进展:ALS/FTD的发病机制、功能和结构。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2021.1892443

Lan Jiang, Tizhong Zhang, Kefeng Lu, Shiqian Qi

引用次数: 5

Phylogenetic reconstruction and evolution of the Rab GTPase gene family in Amoebozoa. 变形虫Rab GTPase基因家族的系统发育重建与进化。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2021.1903794

Alfredo L Porfírio-Sousa, Alexander K Tice, Matthew W Brown, Daniel J G Lahr

{"title":"Phylogenetic reconstruction and evolution of the Rab GTPase gene family in Amoebozoa.","authors":"Alfredo L Porfírio-Sousa, Alexander K Tice, Matthew W Brown, Daniel J G Lahr","doi":"10.1080/21541248.2021.1903794","DOIUrl":"https://doi.org/10.1080/21541248.2021.1903794","url":null,"abstract":"Rab GTPase is a paralog-rich gene family that controls the maintenance of the eukaryotic cell compartmentalization system. Diverse eukaryotes have varying numbers of Rab paralogs. Currently, little is known about the evolutionary pattern of Rab GTPase in most major eukaryotic 'supergroups'. Here, we present a comprehensive phylogenetic reconstruction of the Rab GTPase gene family in the eukaryotic 'supergroup' Amoebozoa, a diverse lineage represented by unicellular and multicellular organisms. We demonstrate that Amoebozoa conserved 20 of the 23 ancestral Rab GTPases predicted to be present in the last eukaryotic common ancestor and massively expanded several 'novel' in-paralogs. Due to these 'novel' in-paralogs, the Rab family composition dramatically varies between the members of Amoebozoa; as a consequence, 'supergroup'-based studies may significantly change our current understanding of the evolution and diversity of this gene family. The high diversity of the Rab GTPase gene family in Amoebozoa makes this 'supergroup' a key lineage to study and advance our knowledge of the evolution of Rab in Eukaryotes.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2021.1903794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9072723","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: 1

Biallelic ELMO3 mutations and loss of function for DOCK-mediated RAC1 activation result in intellectual disability. 双等位基因ELMO3突变和dock介导的RAC1激活功能丧失导致智力残疾。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2021.1888557

Viviane Tran, Marie-Anne Goyette, Mónica Martínez-García, Ana Jiménez de Domingo, Daniel Martín Fernández-Mayoralas, Ana Laura Fernández-Perrone, Pilar Tirado, Beatriz Calleja-Pérez, Sara Álvarez, Jean-François Côté, Alberto Fernández-Jaén

{"title":"Biallelic ELMO3 mutations and loss of function for DOCK-mediated RAC1 activation result in intellectual disability.","authors":"Viviane Tran, Marie-Anne Goyette, Mónica Martínez-García, Ana Jiménez de Domingo, Daniel Martín Fernández-Mayoralas, Ana Laura Fernández-Perrone, Pilar Tirado, Beatriz Calleja-Pérez, Sara Álvarez, Jean-François Côté, Alberto Fernández-Jaén","doi":"10.1080/21541248.2021.1888557","DOIUrl":"https://doi.org/10.1080/21541248.2021.1888557","url":null,"abstract":"The engulfment and cell motility 3 (ELMO3) protein belongs to the ELMO-family of proteins. ELMO proteins form a tight complex with the DOCK1-5 guanine nucleotide exchange factors that regulate RAC1 spatiotemporal activation and signalling. DOCK proteins and RAC1 are known to have fundamental roles in central nervous system development. Here, we searched for homozygous or compound heterozygous mutations in the ELMO3 gene in 390 whole exomes sequenced in trio in individuals with neurodevelopmental disorders compatible with a genetic origin. We found a compound heterozygous mutation in ELMO3 (c.1153A>T, p.Ser385Cys and c.1009 G > A, p.Val337Ile) in a 5 year old male child with autism spectrum disorder (ASD) and developmental delay. These mutations did not interfere with the formation of an ELMO3/DOCK1 complex, but markedly impaired the ability of the complex to promote RAC1-GTP-loading. Consequently, cells expressing DOCK1 and either of the ELMO3 mutants displayed impaired migration and invasion. Collectively, our results suggest that biallelic loss-of-function mutations in ELMO3 may cause a developmental delay and provide new insight into the role of ELMO3 in neurodevelopmental as well as the pathological consequences of ELMO3 mutations.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2021.1888557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089210","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: 3

Regulation of Leukaemia Associated Rho GEF (LARG/ARHGEF12). 白血病相关Rho-GEF（LARG/ARGGEF12）的调节。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2021.1951590

Neda Z Ghanem, Michelle L Matter, Joe W Ramos

引用次数: 7

Rab3a, a small GTP-binding protein, is required for the stabilization of the murine leukaemia virus Gag protein. Rab3a是一种小的gtp结合蛋白，是稳定小鼠白血病病毒Gag蛋白所必需的。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2021.1939631

Mai Izumida, Katsura Kakoki, Hideki Hayashi, Toshifumi Matsuyama, Yoshinao Kubo

{"title":"Rab3a, a small GTP-binding protein, is required for the stabilization of the murine leukaemia virus Gag protein.","authors":"Mai Izumida, Katsura Kakoki, Hideki Hayashi, Toshifumi Matsuyama, Yoshinao Kubo","doi":"10.1080/21541248.2021.1939631","DOIUrl":"https://doi.org/10.1080/21541248.2021.1939631","url":null,"abstract":"We recently identified a CD63-interacting protein to understand the role of CD63 in virion production of the human immunodeficiency virus type 1, and we have found that Rab3a forms a complex with CD63. In this study, we analysed the effect of Rab3a on virion production of the murine leukaemia virus (MLV), which is another member of the retrovirus family. We found that Rab3a silencing induced lysosomal degradation of the MLV Gag protein, and recovery of the Rab3a expression restored the level of the Gag protein through a complex formation of MLV Gag and Rab3a, indicating that Rab3a is required for MLV Gag protein expression. In contrast, CD63 silencing decreased the infectivity of released virions but had no effect on virion production, indicating that CD63 facilitates the infectivity of released MLV particles. Although Rab3a induced CD63 degradation in uninfected cells, the complex of MLV Gag and Rab3a suppressed the Rab3a-mediated CD63 degradation in MLV-infected cells. Finally, we found that the MLV Gag protein interacts with Rab3a to stabilize its own protein and CD63 that facilitates the infectivity of released MLV particles. Considering the involvement of Rab3a in lysosome trafficking to the plasma membrane, it may also induce cell surface transport of the MLV Gag protein.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21541248.2021.1939631","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10579182","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: 1

KRAS G12C fragment screening renders new binding pockets. KRAS G12C片段筛选生成新的结合袋。

Small GTPases Pub Date : 2022-01-01 Epub Date: 2021-09-24 DOI: 10.1080/21541248.2021.1979360

Magali Mathieu, Valérie Steier, Florence Fassy, Cécile Delorme, David Papin, Bruno Genet, Francis Duffieux, Thomas Bertrand, Laure Delarbre, Hélène Le-Borgne, Annick Parent, Patrick Didier, Jean-Pierre Marquette, Maryse Lowinski, Jacques Houtmann, Annabelle Lamberton, Laurent Debussche, Rak Alexey

{"title":"KRAS G12C fragment screening renders new binding pockets.","authors":"Magali Mathieu, Valérie Steier, Florence Fassy, Cécile Delorme, David Papin, Bruno Genet, Francis Duffieux, Thomas Bertrand, Laure Delarbre, Hélène Le-Borgne, Annick Parent, Patrick Didier, Jean-Pierre Marquette, Maryse Lowinski, Jacques Houtmann, Annabelle Lamberton, Laurent Debussche, Rak Alexey","doi":"10.1080/21541248.2021.1979360","DOIUrl":"https://doi.org/10.1080/21541248.2021.1979360","url":null,"abstract":"KRAS genes belong to the most frequently mutated family of oncogenes in cancer. The G12C mutation, found in a third of lung, half of colorectal and pancreatic cancer cases, is believed to be responsible for a substantial number of cancer deaths. For 30 years, KRAS has been the subject of extensive drug-targeting efforts aimed at targeting KRAS protein itself, but also its post-translational modifications, membrane localization, protein-protein interactions and downstream signalling pathways. So far, most KRAS targeting strategies have failed, and there are no KRAS-specific drugs available. However, clinical candidates targeting the KRAS G12C protein have recently been developed. MRTX849 and recently approved Sotorasib are covalent binders targeting the mutated cysteine 12, occupying Switch II pocket.Herein, we describe two fragment screening drug discovery campaigns that led to the identification of binding pockets on the KRAS G12C surface that have not previously been described. One screen focused on non-covalent binders to KRAS G12C, the other on covalent binders.","PeriodicalId":22139,"journal":{"name":"Small GTPases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923024/pdf/KSGT_13_1979360.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39444572","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: 7

Allosteric regulation of GRB2 modulates RAS activation. GRB2的变构调控可调节RAS的激活。

Small GTPases Pub Date : 2022-01-01 DOI: 10.1080/21541248.2022.2089001

Neda S Kazemein Jasemi, Mohammad R Ahmadian

引用次数: 1