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Analysis and Review of Downregulated actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

Journal of Biosciences and Medicines 2024年第4期12卷 89-115页

作者： Hala M. Abdel Mageed Praveen Sahu Raji Sundararajan School of Engineering Technology Purdue University West Lafayette USA National Institute of Standards Al Haram Egypt

actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.

关键词： Non-Small Cell Lung Cancer NSCLC actin actin Cytoskeletal Proteins Focal Adhesion KEEG Pathway

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Dietary xylo‑oligosaccharides and arabinoxylans improved growth efficiency by reducing gut epithelial cell turnover in broiler chickens

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1325-1335页

作者： Carla Castro Shahram Niknafs Gemma Gonzalez‑Ortiz Xinle Tan Michael R.Bedford Eugeni Roura Centre for Nutrition and Food Sciences Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandSt LuciaQLD 4072Australia AB Vista MarlboroughWiltshire SN84ANUK

Background One of the main roles of the intestinal mucosa is to protect against environmental hazards.Supple-mentation of xylo-oligosaccharides(XOS)is known to selectively stimulate the growth of beneficial intestinal bacteria and improve gut health and function in chickens.XOS may have an impact on the integrity of the intestinal epithelia where cell turnover is critical to maintain the compatibility between the digestive and barrier functions.The aim of the study was to evaluate the effect of XOS and an arabinoxylan-rich fraction(AXRF)supplementation on gut func-tion and epithelial integrity in broiler chickens.Methods A total of 128 broiler chickens(Ross 308)were assigned into one of two different dietary treatments for a period of 42 d:1)control diet consisting of a corn/soybean meal-based diet;or 2)a control diet supplemented with 0.5%XOS and 1%AXRF.Each treatment was randomly distributed across 8 pens(n=8)with 8 chickens each.Feed intake and body weight were recorded weekly.On d 42,one male chicken per pen was selected based on aver-age weight and euthanized,jejunum samples were collected for proteomics analysis.Results Dietary XOS/AXRF supplementation improved feed efficiency(Pactin polymerization pathway.Put-ting the two main pathways together,XOS/AXRF supplementation may decrease around 19%the energy required for the maintenance of the gastrointestinal tract.Conclusions Dietary XOS/AXRF supplementation improved growth efficiency by reducing epithelial cell migr

关键词： actin Arabinoxylans Broiler Cell turnover Energy metabolism Jejunum Xylo-oligosaccharides

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The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

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Neural Regeneration Research 2025年第1期20卷 209-223页

作者： Shi-Yan Sun Lingyun Nie Jing Zhang Xue Fang Hongmei Luo Chuanhai Fu Zhiyi Wei Ai-Hui Tang Hefei National Research Center for Physical Sciences at the Microscale CAS Key Laboratory of Brain Function and DiseaseMinistry of Education Key Laboratory for Membrane-less Organelles and Cellular DynamicsDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Institute of Artificial Intelligence Hefei Comprehensive National Science CenterHefeiAnhui ProvinceChina CAS Center for Excellence in Molecular Cell Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurobiology School of Life SciencesSouthern University of Science and TechnologyShenzhenGuangdong ProvinceChina Brain Research Center Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

关键词： actin cytoskeleton dendrite KANK1 KIF21A microtubule spine morphology spine synaptic plasticity talin1

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Bioprocess-inspired actin Biomineralized Hematite Mesocrystals for Energy Storage

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Journal of Wuhan University of Technology(Materials Science) 2023年第6期38卷 1299-1303页

作者： XU Wei ZHAO Chao XIE Jingjing WANG Rongjie Tianjin Institute of Power Sources Tianjin 300384China CETC LAN TIAN Technology Co. Ltd.Tianjin 300384China State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhan 430070China

Biomineralization is a biological process of synthesizing inorganic minerals within organisms.It has been found that intracellular proteins are involved in the room temperature synthesis process of anatase Ti O2in living mussels.Here,we used intracellular actin to synthesize hematite by biomineralization.Biomineralized hematite has a nano spindle structure with a particle size of approximately 150 nm.The microstructure indicates that the prepared hematite is a mesocrystals composed of ordered arrangement and assembly of primary nanoparticles.In addition,hematite mesocrystals exhibit good lithium storage performance as electrode materials for lithium batteries.The discharge specific capacity of the battery remained at 560.7 m Ah·g^(-1)after 130 cycles at a current density of 200 m A·g^(-1).This work expands the synthesis methods of hematite by biomineralization,and provides a new strategy for preparing inorganic materials by intracellular proteins.

关键词： actin hematite biomineralization mesocrystals lithium battery

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LINC complex independent perinuclear actin organization and cell migration

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BIOCELL 2022年第4期46卷 931-935页

作者： ANDREA FRACCHIA GABI GERLITZ Department of Molecular Biology Faculty of Life Sciences and Ariel Center for Applied Cancer ResearchAriel UniversityAriel40700Israel Department of Bone Marrow Transplantation and Cancer Immunotherapy Hadassah Medical OrganizationJerusalem91120Israel

The link of the metazoan nucleus to the actin cytoskeleton is highly important for actin polymerization and migration of multiple cell types as well as for mechanotransduction and even affects the cellular transcriptome.Several mechanisms of organization of actin filaments next to the nuclear envelope have been identified.Among these mechanisms the most studied one is the Linker of nucleoskeleton and cytoskeleton(LINC)complex-dependent perinuclear actin organization.However,recently additional mechanisms have been identified:an actin-related protein-2/3(Arp2/3)-dependent perinuclear actin polymerization during migration of dendritic cells and a perinuclear actin rim that is formed in response to external force application or migration cues.In parallel,there are also reports on cancer cells that migrate in a LINC complex independent manner and on cancers with reduced expression of the LINC complex components.Thus,suggesting that LINC complex independent migration may be associated with tumour formation.

关键词： Cell migration actin Lamins Nuclear envelope Cancer

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actin Polymerization Mediated by AtFH5 Directs the Polarity Establishment and Vesicle Trafficking for Pollen Germination in Arabidopsis

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Molecular Plant 2018年第11期11卷 1389-1399页

作者： Chang Liu Yi Zhang Haiyun Ren Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education College of Life ScienceBeijing Normal UniversityBeijing 100875China

The process of pollen germination is crucial for flowering plant reproduction,but the mechanisms through which pollen grains establish polarity and select germination sites are not well understood.In this study,we report that a formin family protein,AtFH5,is localized to the vesicles and rotates ahead of Lifeact-mEGFPlabeled actin filaments during pollen germination.The translocation of AtFH5 to the plasma membrane initiates the assembly of a collar-like actin structure at the prospective germination site prior to germination. Genetic and pharmacological evidence further revealed an interdependent relationship between the mobility of AtFH5-1 abeled vesicles and the polymerization of actin filaments:vesicle-localized AtFH5 promotes actin assembly,and the polymerization and elongation of actin filaments,in turn,is essential for the mobility of AtFH5-1 abeled vesicles in pollen grains.Taken together,our work revealed a molecular mechanism underlying the polarity establishment and vesicle mobility during pollen germination.

关键词： Chinese cabbage Pollen germination Polarity establishment Vesicle trafficking actin Formin

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Preliminarily Investigating the Polymorphism of Self-organized actin Filament in Vitro by Atomic Force Microscope

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Acta Biochimica et Biophysica Sinica 2004年第9期36卷 637-643页

作者： Jun ZHANG1,2, Yuan-Liang WANG1*, Xin-Yong Chen3, Chuang-Long HE1, Chao CHENG1, and Yang CAO1 1Key Lab of Biomechanics & Tissue Engineering, Chongqing University, Chongqing 400044, China Biology Department, Chongqing University of Medicine Sciences, Congqing 400016, China 3Laboratory of Biophysics and Surface Analysis, University of Nottingham, Nottingham NG7 2RD, United Kingdom Key Lab of Biomechanics & Tissue Engineering Chongqing UniversityChongqing 400044 China Biology Department Chongqing University of Medicine SciencesCongqing 400016 China Laboratory of Biophysics and Surface Analysis University of NottinghamNottingham NG7 2RD United Kingdom

With the atomic force microscope (AFM), we preliminarily investigated the large-scale structure of actin filaments formed in low concentration protein solution (5 μg/ml) via self-organization without the presence of any F-actin dynamic interfering factors (such as phalloidin)in vitro. It was found that the G-actin could be polymerized into ordered filamentous structures with different diameter from the slimmest filament of single F-actin to giant filament in tree-like branched aggregates. The observed polymerized actin filaments, to which our most intense attention was attracted, was discretely distributed and showed obvious polymorphism distinctly different from those in the presence of phalloidin or actin binding proteins (fimbrin, gelsolin, etc.) in previous experiments. Latter structures were mainly composed of single F-actin and/or multifilaments clearly consisting of several single F-actin. The experimental results clearly demonstrated that non-interference with the F-actin intrinsic dynamics in self-organizing could lead to the polymorphism of actin filamentous structures, and further analysis implied that the disturbance of normal F-actin dynamics by many factors could prevent the emergence of structural polymorphism, more often than not, give rise to formation of specific structures instead and different interference would bring about various particular structures under certain conditions.

关键词： actin self-organization filamentous structure polymorphism atomic force microscope

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LRRK2 regulates actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis

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Journal of Molecular Cell Biology 2022年第1期14卷 21-31页

作者： Zhen-Nan Pan Jing-Cai Liu Jia-Qian Ju Yue Wang Shao-Chen Sun College of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210095China

Leucine-rich-repeat kinase 2 (LRRK2) belongs to the Roco GTPase family and is a large multidomain protein harboring both GTPase and kinase activities. LRRK2 plays indispensable roles in many processes, such as autophagy and vesicle trafficking in mitosis. In this study, we showed the critical roles of LRRK2 in mammalian oocyte meiosis. LRRK2 is mainly accumulated at the meiotic spindle periphery during oocyte maturation. Depleting LRRK2 led to the polar body extrusion defects and also induced large polar bodies in mouse oocytes. Mass spectrometry analysis and co-immunoprecipitation results showed that LRRK2 was associated with several actin-regulating factors, such as Fascin and Rho-kinase (ROCK), and depletion of LRRK2 affected the expression of ROCK, phosphorylated cofilin, and Fascin. Further analysis showed that LRRK2 depletion did not affect spindle organization but caused the failure of spindle migration, which was largely due to the decrease of cytoplasmic actin filaments. Moreover, LRRK2 showed a similar localization pattern to mitochondria, and LRRK2 was associated with several mitochondria-related proteins. Indeed, mitochondrial distribution and function were both disrupted in LRRK2-depleted oocytes. In summary, our results indicated the critical roles of LRRK2 in actin assembly for spindle migration and mitochondrial function in mouse oocyte meiosis.

关键词： actin spindle LRRK2 oocyte meiosis

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The actin-bundling protein Fascin-1 modulates ciliary signalling

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Journal of Molecular Cell Biology 2023年第4期15卷 1-16页

作者： Lena Brücker Stefanie Kornelia Becker Vanessa Maissl Gregory Harms Maddy Parsons Helen Louise May-Simera Cilia Cell Biology Institute of Molecular PhysiologyJohannes Gutenberg University Mainz55128 MainzGermany Imaging Core Facility Cell Biology UnitUniversity Medical CentreJohannes Gutenberg University Mainz55101 MainzGermany Randall Centre for Cell and Molecular Biophysics King's College LondonLondon SE11ULUK

Primary cilia are microtubule-based cell organelles important for cellular communication. Since they are involved in the regulation of numerous signalling pathways, defects in cilia development or function are associated with genetic disorders, collectively called ciliopathies. Besides their ciliary functions, recent research has shown that several ciliary proteins are involved in the coordination of the actin cytoskeleton. Although ciliary and actin phenotypes are related, the exact nature of their interconnection remains incompletely understood. Here, we show that the protein BBS6, associated with the ciliopathy Bardet–Biedl syndrome, cooperates with the actin-bundling protein Fascin-1 in regulating filopodia and ciliary signalling. We found that loss of Bbs6 affects filopodia length potentially via attenuated interaction with Fascin-1. Conversely, loss of Fascin-1 leads to a ciliary phenotype, subsequently affecting ciliary Wnt signalling, possibly in collaboration with BBS6. Our data shed light on how ciliary proteins are involved in actin regulations and provide new insight into the involvement of the actin regulator Fascin-1 in ciliogenesis and cilia-associated signalling. Advancing our knowledge of the complex regulations between primary cilia and actin dynamics is important to understand the pathogenic consequences of ciliopathies.

关键词： cilia actin Wnt signalling ciliopathy Bardet–Biedl syndrome filopodia

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Plastins:versatile modulators of actin organization in (patho)physiological cellular processes

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Acta Pharmacologica Sinica 2005年第7期26卷 769-779页

作者： Veerle DELANOTE Jo■l VANDEKERCKHOVE Jan GETTEMANS Faculty of Medicine and Health Sciences Albert Baertsoenkaai 3 B-9000 Ghent Belgium Department of Medical Protein Research Flanders Interuniversity Institute for Biotechnology(VIB) Ghent University Faculty of Medicine and Health Sciences Albert Baertsoenkaai 3 B-9000 Ghent Department of Medical Protein Research Flanders Interuniversity Institute for Biotechnology(VIB) Belgium Ghent University Faculty of Medicine and Health Sciences Albert Baertsoenkaai 3 B-9000 Ghent Belgium Department of Medical Protein Research Flanders Interuniversity Institute for Biotechnology(VIB) Ghent University

Many actin-binding proteins are expressed in eukaryotic cells.These polypep-tides assist in stabilizing and rearranging the organization of the actin cytoskel-eton in response to external stimuli,or during cell migration and adhesion.Herewe review a particular set of actin-binding proteins called plastins.Plastins(alsocalled fimbrins)belong to a subclass of actin-binding proteins known as actinbundling proteins.Three isoforms have been characterized in mammals:T-plastinis expressed in cells from solid tissue,whereas L-plastin occurs predominantly inhematopoietic cells.The third isoform,I-plastin,is specifically expressed in thesmall intestine,colon and kidney.These proteins share the unique property ofcross-linking actin filaments into fight bundles.Although plastins are primarilyinvolved in regulation of the actin cytoskeleton,they possess some uniquefeatures.For instance,they are implicated in invasion by pathogenic bacteriasuch as Shigellaflexneri and Salmonella typhimurium.Also,L-plastin plays animportant role in leukocyte function.T-plastin,on the other hand,is possiblyinvolved in DNA repair.Finally,both T-and L-plastin are implicated in severaldiseases,and L-plastin is considered to be a valuable marker for cancer.

关键词： actin actin-binding protein plastin cytoskeleton

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