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PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-Da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare Pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal CA1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder actin cytoskeleton Animal behavior

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Mutual regulation between Hippo signaling and actin cytoskeleton

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Protein & Cell 2013年第12期4卷 904-910页

作者： Yurika Matsui Zhi-Chun Lai I ntercollege Graduate Degree Program in Cell and Developmental Biology The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biology The Pennsylvania State UniversityUniversity ParkPA 16802USA Department of Biochemistry and Molecular Biology The Pennsylvania State UniversityUniversity ParkPA 16802USA

Hippo signaling plays a crucial role in growth control and tumor suppression by regulating cell proliferation,apoptosis,and *** Hippo signaling is regulated has been under extensive *** the past three years,an increasing amount of data have supported a model of actin cytoskeleton blocking Hippo signaling activity to allow nuclear accumulation of a downstream effector,Yki/Yap/*** the other hand,Hippo signaling negatively regulates actin cytoskeleton *** review p rovides insight on the mutual regulatory mechanisms between Hippo signaling and actin cytoskeleton for a tight control of cell behaviors during animal development,and points out outstanding questions for further investigations.

关键词： Hippo signaling actin cytoskeleton negative feedback growth control development

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Effects of dexamethasone and HA1077 on actin cytoskeleton and β-catenin in cultured human trabecular meshwork cells

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International Journal of Ophthalmology(English edition) 2016年第10期9卷 1376-1380页

作者： Jie Peng Xiao-Yun Feng Zi-Meng Ye Qian Luo Yi-Lian Cheng Zheng-Zheng Wu Chun-Tao Lei Bo Gong Department of Ophthalmology Sichuan Academy of Medical Sciences & Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of China Sichuan Provincial Key Laboratory for Human Disease Gene Study Sichuan Academy of Medical Sciences & Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of China Institute of Laboratory Medicine Sichuan Academy of Medical Sciences & Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of China

AIM：To investigate the effects of dexamethasone（DEX） and 1-（5-isoquinolinesulfonyl）-homopiperazine（HA1077） on actin cytoskeleton and β-catenin in cultured human trabecular meshwork（HTM） ***： The HTM cells were separated from human eyeball and cultured in *** were divided into control group,DEX（1×10^-6mol/L） group,HA1077（3×10^-5mol/L）group,and DEX（1×10^-6mol/L） and HA1077（3×10^-5mol/L）*** cytoskeleton and β-catenin in HTM cells of the four groups were examined by immunofluorescence and Western blot ***： In DEX group,there were reorganization of actin cytoskeleton and formation of cross linked actin networks（CLANs）,which were partially reversed in DEX and HA1077 *** treatment also induced an increased expression of β-catenin,which was obviously reduced in DEX and HA1077 ***,the cultured HTM cells in HA1077 group had lower expression of β-catenin than that in the control group. CONCLUSION： Our results show that HA1077 can reverse the changes of actin organization and expression of β-catenin induced by DEX in cultured HTM cells,suggesting that HA1077 may play an important role in increasing outflow and reducing intraocular pressure.

关键词： HA1077 trabecular meshwork cell dexamethasone actin cytoskeleton β-catenin

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The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor

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Frontiers in Biology 2013年第5期8卷 475-485页

作者： Chaohong LIU Margaret K. FALLEN Heather MILLER Arpita UPADHYAYA Wenxia SONG Department of Cell Biology & Molecular Genetics University of Maryland College Park MD 20742 USA Department of Physics University of Maryland College Park MD 20742 USA Division of Immunology Children's Hospital of Chongqing Medical University Chongqing 400014 China

The B cell antigen receptor （BCR） is the sensor on the B cell surface that surveys foreign molecules （antigen） in our bodies and activates B cells to generate antibody responses upon encountering cognate antigen. The binding of antigen to the BCR induces signaling cascades in the cytoplasm, which provides the first signal for B cell activation. Subsequently, BCRs internalize and target bound antigen to endosomes, where antigen is processed into T cell recognizable forms. T helper cells generate the second activation signal upon binding to antigen presented by B cells. The optimal activation of B cells requires both signals, thereby depending on the coordination of BCR signaling and antigen transport functions. Antigen binding to the BCR also induces rapid remodeling of the cortical actin network of B cells. While being initiated and controlled by BCR signaling, recent studies reveal that this actin remodeling is critical for both the signaling and antigen processing functions of the BCR, indicating a role for actin in coordinating these two pathways. Here we will review previous and recent studies on actin reorganization during BCR activation and BCR- mediated antigen processing, and discuss how actin remodeling translates BCR signaling into rapid antigen uptake and processing while providing positive and negative feedback to BCR signaling.

关键词： actin cytoskeleton endocytosis signal transduction receptor

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Regulation of actin cytoskeleton via photolithographic micropatterning

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Journal of Innovative Optical Health Sciences 2023年第2期16卷 50-57页

作者： Fulin Xing Haimei Zhang Mengyu Li Hao Dong Xuehe Ma Shiyu Deng Fen Hu Imshik Lee Leiting Pan Jingjun Xu The Key Laboratory of Weak-Light Nonlinear Photonics of Education Ministry School of Physics and TEDA Institute of Applied Physics Nankai University Tianjin 300071 P.R.China State Key Laboratory of Medicinal Chemical Biology Frontiers Science Center for Cell Responses College of Life Sciences Nankai University Tianjin 300071P.R.China Collaborative Innovation Center of Extreme Optics Shanxi University Taiyuan Shanxi 030006P.R.China Shenzhen Research Institute of Nankai University Shenzhen Guangdong 518083P.R.China

actin cytoskeleton plays crucial roles in various cellular *** matrix(ECM)can modulate cell morphology by remodeling the internal *** define how geometry of ECM regulates the organization of actin cytoskeleton,we plated individual NIH 3T3 cells on micropatterned substrates with distinct shapes and *** was found that the stress fibers could form along the nonadhesive edges of T-shaped pattern,but were absent from the opening edge of V-shaped pattern,indicating that the organization of actin cytoskeleton was dependent on the mechanical ***,a secondary actin ring was observed on 50μm circular pattern while did not appear on 30μm and 40μm pattern,showing a size-dependent organization of actin ***,osteoblasts,MDCK and A549 cells exhibited distinct organization of actin cytoskeleton on T-shaped pattern,suggesting a cell-type specificity in arrangement of actin ***,our findings brought novel insight into the organization of actin cytoskeleton on micropatterned environments.

关键词： actin cytoskeleton photolithography micropatterning extracellular matrix

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Scinderin promotes glioma cell migration and invasion via remodeling actin cytoskeleton

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World Journal of Clinical Oncology 2024年第1期15卷 32-44页

作者： Xin Lin Zhao Zhao Shu-Peng Sun Wei Liu Department of Neurosurgery Tianjin Huanhu HospitalTianjin 300000China

BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor *** cytoskeletal rearrangement is an essential event of tumor cell *** actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several *** To investigate the role and mechanism of SCIN in *** The expression and clinical significance of SCIN in glioma were analyzed based on public *** expression was examined using real-time quantitative polymerase chain reaction and Western *** silencing was performed using short hairpin RNA *** viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin *** SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate ***,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 ***,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 *** SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma *** study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.

关键词： Glioma Scinderin actin cytoskeleton RhoA/FAK signaling Depolymerization

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The formation of autophagosomes at ER-PM contact sites in concert with the actin cytoskeleton and the endocytic machinery

The formation of autophagosomes at ER-PM contact sites in co...

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2018全国植物生物学大会

作者： Pengwei Wang Roman Pleskot Jingze Zang Joanna Winkler Jie Wang Klaas Yperman Jinli Gong Kun Wang Yajie Guan Patrick Duckney Christine Richardson Michael VANDorpe Jindriska Fiserova Daniel Van Damme Patrick J.Hussey Key Laboratory of Horticultural Plant Biology (MOE) College of Horticulture and Forestry SciencesHuazhong Agricultural University Department of Biosciences Durham University Ghent University Department of Plant Biotechnology and Bioinformatics Department of Biology of the Cell Nucleus Institute of Molecular Genetics CAS

Plants evolved their own strategy to form the essential link between the endoplasmic reticulum(ER) and the plasma membrane(PM) through a complex including NET3 C and VAP27(Wang et al 2014,Curr Biol).However,the function of plant ER-PM contact sites has not been fully *** this study,we have identified a function for ER-PM contact sites(EPCS) in plants and that is in the autophagosome biogenesis pathway,in concert with actin cytoskeleton and the Arabidopsis EH ***1 and AtEH2 are components of the endocytic TPLATE complex which is known to be essential for endocytosis in plants(Gadeyne et al.,2014,Cell).Both proteins(from now on termed AtEH/Pan1) share high sequence similarity with the yeast ARP2/3 complex activator,Pan1 *** AtEH/Panl proteins localise to the plasma membrane and autophagosomes,and their autophagosome membrane recruitment requires its N-terminal EH domains which interact with *** induction of autophagy,AtEH/Pan1 proteins recruit TPC and AP-2 subunitsand ARP2/3 proteins onto the autophagosome *** expression of AtEH1/Pan1 boosts autophagosome formation and suggest independent and redundant pathways for actin mediated autophagy in ***,AtEH/Pan1 regulated autophagosomes are found associated with EPCS where AtEH/Panl interacts with *** knock-down expression of either AtEH/Pan1 or VAP27-1 are more susceptible to nutrient depleted conditions,indicating defective *** conclusion,our results suggest that AtEH/Pan1 proteins regulate an autophagosome-dependent degradation pathway which starts at the EPCS through its interaction with VAP27-1 and merges with endocytic pathways.

关键词： Membrane contact sites Autophagy actin cytoskeleton Panlp TPLATE

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The actin cytoskeleton Controls FcγRIIB-Mediated Inhibition of B-Cell Signaling

The Actin Cytoskeleton Controls FcγRIIB-Mediated Inhibition...

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第十三届全国免疫学学术大会

作者： Zhou Shu Xiaodong Zhao Children’s Hospital of Chongqing Medical University

FcgRIIB is a major inhibitory coreceptor of B cell receptor(BCR), and its deficiency leads to B cell autoimmunity. Upon colligated with the BCR by immune complexes(ICs), this coreceptor activates SH2-containing inositol-5 phosphatase(SHIP) and inhibits BCR clustering in lipid rafts. However, the molecular mechanisms underlying FcgRIIB-mediated inhibition of BCR activation remain elusive. This study reveals a critical role of the actin cytoskeleton in FcgRIIB-mediated inhibition. Upon interacting with ICs tethered to lipid bilayers, an actomyosin ring is quickly formed surrounding the B cell membrane region interacting with the lipid bilayer(contact zone). Perturbing the actomyosin ring, by myosin inhibitors or B cell-specific gene knockout of non-muscle myosin IIA(NMIIA) or neuronal Wiskott-Aldrich syndrome protein(N-WASP), releases B cell spreading, BCR clustering and signaling from the inhibition by FcgRIIB. Using conditional gene knockout mice, we further show that NMIIA is recruited to the B cell contact zone in an SHIP-dependent manner, while N-WASP-mediated actin remodeling organizes NMIIA and actin into a ring. Surprisingly, WASP-mediated actin dynamics is required for the FcgRIIB-induced activation of SHIP but not the formation of the actomyosin ring. Our results suggest that FcgRIIB-triggered signaling induces unique actin remodeling involving NMII, WASP, and N-WASP, which limits B cell morphological changes and BCR lateral mobility and enhances the activation of inhibitory signaling. These data potentially provide a mechanistic explanation for the elevated autoantibody levels caused by WASP or N-WASP deficiency.

关键词： actin cytoskeleton FcγRIIB B cell signaling

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Effects of extracts from Renshen(Radix Ginseng), Sanqi(Radix Notoginseng), and Chuanxiong(Rhizoma Chuanxiong) on F-actin in senescent microvascular endothelial cells

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Journal of Traditional Chinese Medicine 2020年第3期40卷 376-385页

作者： Wang Qiang Yang Jing Lei Yan Xiu Chengkui Huo Yanming Shi Hang Department of Cardiology Wangjing HospitalChina Academy of Chinese Medical SciencesBeijing 100102China Graduate School of Beijing University of Chinese Medicine Beijing 100029China Experimental Research Center China Academy of Chinese Medical SciencesBeijing 100700China

OBJECTIVE: To investigate the effects of extracts from Renshen(Radix Ginseng), Sanqi(Radix Notoginseng), and Chuanxiong(Rhizoma Chuanxiong) on the endothelial actin cytoskeleton in senescent human cardiac microvascular endothelial cells(HCMECs), and to propose the possible mechanism underlying the ***: Lentiviral mediated RNA interference was applied to a replicative senescent HCMEC model by knocking down heat shock protein 27(HSP27)gene. Cells were treated with extracts from Renshen(Radix Ginseng), Sanqi(Radix Notoginseng), and Chuanxiong(Rhizoma Chuanxiong) at final concentrations of 50, 100, and 200 mg/L, respectively and with 10 μM resveratrol for 48 h. Untreated cells were used as controls. Senescence was detected by senescence β-galactosidase staining and cell proliferation was analyzed by cell counting kit-8 *** nitric oxide levels were detected by nitrate reductase. Morphological changes of F-actin and G-actin were observed by laser scanning confocal microscopy. Protein and gene expression of Factin and HSP27 was detected by western ***: Compared with the control group, the proportion of senescent HSP27 shRNA cells treated with the extracts was decreased and their proliferation was increased. In the extract intervention group, F-actin around the cell periphery became irregular and jagged fractures formed gradually and then dissipated. Moreover, some dynamic actin stress fiber filaments appeared. The G-actin stretched to the cell periphery and punctate staining was scattered in the cytoplasm. In addition, the mean optical density value of F/G-actin was decreased significantly and the protein expression of F-actin was ***: The extracts delayed microvascular endothelial cell senescence by downregulating the expression of F-actin through HSP27.

关键词： Endothelial cells Aging actin cytoskeleton HSP27 heat-shock proteins Renshen(Radix Ginseng) Sanqi(Radix Notoginseng) Chuanxiong(Rhizoma Chuanxiong)

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Plant villins: Versatile actin regulatory proteins

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Journal of Integrative Plant Biology 2015年第1期57卷 40-49页

作者： Shanjin Huang Xiaolu Qu Ruihui Zhang Key Laboratory of Plant Molecular Physiology Institute of Botany the Chinese Academy of Sciences

Regulation of actin dynamics is a central theme in cell biology that is important for different aspects of cell physiology. Villin, a member of the villin/gelsolin/fragmin superfamily of proteins, is an important regulator of actin. Villins contain six gelsolin homology domains （G1-G6） and an extra headpiece domain. In contrast to their mammalian counterparts, plant villins are expressed widely, implying that plant villins play a more general role in regulating actin dynamics. Some plant villins have a defined role in modifying actin dynamics in the pollentube; most of their in vivo activities remain to be ascertained. Recently, our understanding of the functions and mechanisms of action for plant villins has progressed rapidly, primarily due to the advent of Arabidopsis thaliana genetic approaches and imaging capabilities that can visualize actin dynamics at the single filament level in vitro and in living plant cells. In this review, we focus on discussing the biochemical activities and modes of regulation of plant villins. Here, we present current understand- ing of the functions of plant villins. Finally, we highlight some of the key unanswered questions regarding the functions and regulation of plant villins for future research.

关键词： actin bundle actin capping actin cytoskeleton filamentsevering villin

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