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Ying Gao, Haiqi Chen, Wing-Yee Lui, Will M Lee, C Yan Cheng
A local axis connects the apical ectoplasmic specialization (ES) at the Sertoli-spermatid interface, the basal ES at the blood-testis barrier (BTB), and the basement membrane across the seminiferous epithelium functionally in rat testes. As such, cellular events that take place simultaneously across the epithelium such as spermiation and BTB remodeling that occur at the apical ES and the basal ES, respectively, at stage VIII of the cycle are coordinated. Herein, laminin α2, a structural component of the basement membrane, was found to regulate BTB dynamics...
April 1, 2017: Endocrinology
Won-Sik Shin, Hyun Jae Shim, Young Hun Lee, Minju Pyo, Jun Sang Park, So Yun Ahn, Seung-Taek Lee
Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma-membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells...
February 18, 2017: Journal of Cellular Biochemistry
Yin Lu, Jianshe Wang, Xuejiang Guo, Shengmin Yan, Jiayin Dai
Perfluorooctanoic acid (PFOA) is an abundant perfluoroalkyl substance widely applied in industrial and consumer products. Among its potential health hazards, testicular toxicity is of major concern. To explore the potential effect of miRNA on post-translational regulation after PFOA exposure, changes in miRNAs were detected via miRNA array. Seventeen miRNAs were differentially expressed (eight upregulated, nine downregulated) in male mouse testes after exposure to 5mg/kg/d of PFOA for 28d (>1.5-fold and P<0...
March 1, 2017: Toxicology and Applied Pharmacology
Elise Delage, Diégo Cordero Cervantes, Esthel Pénard, Christine Schmitt, Sylvie Syan, Andrea Disanza, Giorgio Scita, Chiara Zurzolo
Tunneling Nanotubes (TNTs) are actin enriched filopodia-like protrusions that play a pivotal role in long-range intercellular communication. Different pathogens use TNT-like structures as "freeways" to propagate across cells. TNTs are also implicated in cancer and neurodegenerative diseases, making them promising therapeutic targets. Understanding the mechanism of their formation, and their relation with filopodia is of fundamental importance to uncover their physiological function, particularly since filopodia, differently from TNTs, are not able to mediate transfer of cargo between distant cells...
December 23, 2016: Scientific Reports
Sai Huang, Cong Feng, Li Chen, Zhi Huang, Xuan Zhou, Bei Li, Li-Li Wang, Wei Chen, Fa-Qin Lv, Tan-Shi Li
BACKGROUND This study aimed to identify the potential key long non-coding RNAs (lncRNAs) and target genes associated with pneumonia using lncRNA sequencing (lncRNA-seq). MATERIAL AND METHODS A total of 9 peripheral blood samples from patients with mild pneumonia (n=3) and severe pneumonia (n=3), as well as volunteers without pneumonia (n=3), were received for lncRNA-seq. Based on the sequencing data, differentially expressed lncRNAs (DE-lncRNAs) were identified by the limma package. After the functional enrichment analysis, target genes of DE-lncRNAs were predicted, and the regulatory network was constructed...
September 24, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Niranjan Jeganathan, Dan Predescu, Jin Zhang, Fei Sha, Cristina Bardita, Monal Patel, Stephen Wood, Jeffrey A Borgia, Robert A Balk, Sanda Predescu
BACKGROUND: The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied. METHODS: Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies...
September 14, 2016: Molecular Cancer
D Fang, H Chen, J Y Zhu, W Wang, Y Teng, H-F Ding, Q Jing, S-B Su, S Huang
Epithelial-mesenchymal transition (EMT) is regarded as a crucial contributing factor to cancer progression. Diverse factors have been identified as potent EMT inducers in ovarian cancer. However, molecular mechanism sustaining EMT of ovarian cancer cells remains elusive. Here we show that the presence of SOS1/EPS8/ABI1 complex is critical for sustained EMT traits of ovarian cancer cells. Consistent with the role of SOS1/EPS8/ABI1 complex as a Rac1-specific guanine nucleotide exchange factor, depleting Rac1 results in the loss of most of mesenchymal traits in mesenchymal-like ovarian cancer cells, whereas expressing constitutively active Rac1 leads to EMT in epithelial-like ovarian cancer cells...
March 2017: Oncogene
Qian Li, Wei Bao, Qiong Fan, Wen-Jing Shi, Zhu-Nan Li, Ying Xu, Dan Wu
Epidermal growth factor receptor pathway substrate 8 (Eps8) has been identified as a novel substrate for epidermal growth factor receptor (EGFR) kinase and is involved in EGFR‑mediated signaling pathways correlated with tumorigenesis, proliferation and metastasis in various cancer types. However, the precise role of Eps8 in cervical cancer metastasis remains to be elucidated. Immunohistochemistry revealed that Eps8 was significantly increased in cervical cancer specimens compared with squamous intraepithelial lesion and normal cervical tissues...
October 2016: Molecular Medicine Reports
Yu-Ting Wang, Chiung-Chun Huang, Yun-Shan Lin, Weu-Fang Huang, Cheng-Yi Yang, Cheng-Che Lee, Che-Ming Yeh, Kuei-Sen Hsu
Epidermal growth factor receptor substrate 8 (Eps8) is a multifunctional protein involved in actin cytoskeleton regulation and is abundantly expressed in many brain regions. However, the functional significance of Eps8 in the brain has only just begun to be elucidated. Here, we demonstrate that genetic deletion of Eps8 (Eps8(-/-)) from excitatory neurons leads to impaired performance in a novel object recognition test. Consistently, Eps8(-/-) mice displayed a deficit in the maintenance of long-term potentiation in the CA1 region of hippocampal slices, which was rescued by bath application of N-methyl-d-aspartate receptor (NMDAR) antagonist 2-amino-5-phosphonopentanoate...
July 19, 2016: Neuropharmacology
Ying Gao, Wing-Yee Lui, Will M Lee, C Yan Cheng
Crumbs homolog 3 (or Crumbs3, CRB3) is a polarity protein expressed by Sertoli and germ cells at the basal compartment in the seminiferous epithelium. CRB3 also expressed at the blood-testis barrier (BTB), co-localized with F-actin, TJ proteins occludin/ZO-1 and basal ES (ectoplasmic specialization) proteins N-cadherin/β-catenin at stages IV-VII only. The binding partners of CRB3 in the testis were the branched actin polymerization protein Arp3, and the barbed end-capping and bundling protein Eps8, illustrating its possible role in actin organization...
2016: Scientific Reports
Jing-Wen Du, Yu-Xin Wang, Wei-Jun Zhou, Chun-Jun Jiang, Xiao-Ling Xie, Hong-Hao Zhang, Yan-Jie He, Yu-Hua Li
OBJECTIVE: To find and identify HLA-A*0201 restricted cytotoxic T lymphocyte (CTL) epitopes from epidermal growth factor pathway substrate number 8 (Eps8) for specific immunotherapy based on Eps8-derived epitopes in clinic. METHODS: Online biological softwares involved C-proteasomal cleavage, MHC class I binding affinity and TAP transport efficiency were used for prediction of HLA-A*0201 restricted epitopes from Eps8. Then, T2-binding assays and peptide/MHC complex stability tests were used to further verify the predicted epitopes...
June 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
Thankiah Sudhaharan, Kai Ping Sem, Hwi Fen Liew, Yuan Hong Yu, Wah Ing Goh, Ai Mei Chou, Sohail Ahmed
Rif induces dorsal filopodia but the signaling pathway responsible for this has not been identified. We show here that Rif interacts with the I-BAR family protein IRTKS (also known as BAIAP2L1) through its I-BAR domain. Rif also interacts with Pinkbar (also known as BAIAP2L2) in N1E-115 mouse neuroblastoma cells. IRTKS and Rif induce dorsal membrane ruffles and filopodia. Dominant-negative Rif inhibits the formation of IRTKS-induced morphological structures, and Rif activity is blocked in IRTKS-knockout (KO) cells...
July 15, 2016: Journal of Cell Science
Mathew D Littlejohn, Kathryn Tiplady, Tania A Fink, Klaus Lehnert, Thomas Lopdell, Thomas Johnson, Christine Couldrey, Mike Keehan, Richard G Sherlock, Chad Harland, Andrew Scott, Russell G Snell, Stephen R Davis, Richard J Spelman
The mammary gland is a prolific lipogenic organ, synthesising copious amounts of triglycerides for secretion into milk. The fat content of milk varies widely both between and within species, and recent independent genome-wide association studies have highlighted a milk fat percentage quantitative trait locus (QTL) of large effect on bovine chromosome 5. Although both EPS8 and MGST1 have been proposed to underlie these signals, the causative status of these genes has not been functionally confirmed. To investigate this QTL in detail, we report genome sequence-based imputation and association mapping in a population of 64,244 taurine cattle...
2016: Scientific Reports
Joseph H R Hetmanski, Egor Zindy, Jean-Marc Schwartz, Patrick T Caswell
Cell migration in 3D microenvironments is fundamental to development, homeostasis and the pathobiology of diseases such as cancer. Rab-coupling protein (RCP) dependent co-trafficking of α5β1 and EGFR1 promotes cancer cell invasion into fibronectin (FN) containing extracellular matrix (ECM), by potentiating EGFR1 signalling at the front of invasive cells. This promotes a switch in RhoGTPase signalling to inhibit Rac1 and activate a RhoA-ROCK-Formin homology domain-containing 3 (FHOD3) pathway and generate filopodial actin-spike protrusions which drive invasion...
May 2016: PLoS Computational Biology
Elisa Tavazzani, Paolo Spaiardi, Valeria Zampini, Donatella Contini, Marco Manca, Giancarlo Russo, Ivo Prigioni, Walter Marcotti, Sergio Masetto
Several genetic mutations affecting the development and function of mammalian hair cells have been shown to cause deafness but not vestibular defects, most likely because vestibular deficits are sometimes centrally compensated. The study of hair cell physiology is thus a powerful direct approach to ascertain the functional status of the vestibular end organs. Deletion of Epidermal growth factor receptor pathway substrate 8 (Eps8), a gene involved in actin remodeling, has been shown to cause deafness in mice...
July 22, 2016: Neuroscience
Seham Ebrahim, Neil J Ingham, Morag A Lewis, Michael J C Rogers, Runjia Cui, Bechara Kachar, Johanna C Pass, Karen P Steel
WHRN (DFNB31) mutations cause diverse hearing disorders: profound deafness (DFNB31) or variable hearing loss in Usher syndrome type II. The known role of WHRN in stereocilia elongation does not explain these different pathophysiologies. Using spontaneous and targeted Whrn mutants, we show that the major long (WHRN-L) and short (WHRN-S) isoforms of WHRN have distinct localizations within stereocilia and also across hair cell types. Lack of both isoforms causes abnormally short stereocilia and profound deafness and vestibular dysfunction...
May 3, 2016: Cell Reports
Haiqi Chen, Dolores D Mruk, Will M Lee, C Yan Cheng
Planar cell polarity (PCP) proteins confer polarization of a field of cells (eg, elongating/elongated spermatids) within the plane of an epithelium such as the seminiferous epithelium of the tubule during spermatogenesis. In adult rat testes, Sertoli and germ cells were found to express PCP core proteins (eg, Van Gogh-like 2 [Vangl2]), effectors, ligands, and signaling proteins. Vangl2 expressed predominantly by Sertoli cells was localized at the testis-specific, actin-rich ectoplasmic specialization (ES) at the Sertoli-spermatid interface in the adluminal compartment and also Sertoli-Sertoli interface at the blood-testis barrier (BTB) and structurally interacted with actin, N-cadherin, and another PCP/polarity protein Scribble...
May 2016: Endocrinology
Kana Aoki, Fumiyo Maeda, Tomoya Nagasako, Yuki Mochizuki, Seiichi Uchida, Junichi Ikenouchi
The actin cytoskeleton usually lies beneath the plasma membrane. When the membrane-associated actin cytoskeleton is transiently disrupted or the intracellular pressure is increased, the plasma membrane detaches from the cortex and protrudes. Such protruded membrane regions are called blebs. However, the molecular mechanisms underlying membrane blebbing are poorly understood. This study revealed that epidermal growth factor receptor kinase substrate 8 (Eps8) and ezrin are important regulators of rapid actin reassembly for the initiation and retraction of protruded blebs...
March 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
Elizabeth I Tang, Will M Lee, C Yan Cheng
Germ cell transport across the seminiferous epithelium during spermatogenesis requires the intricate coordination of cell junctions, signaling proteins, and both actin- and microtubule (MT)-based cytoskeletons. Although the involvement of cytoskeletons in germ cell transport has been suggested, the precise mechanism(s) remains elusive. Based on growing evidence that actin and MT interactions underlie fundamental cellular processes, such as cell motility, it is unlikely that actin- and MT-based cytoskeletons work independently to regulate germ cell transport in the testis...
April 2016: Endocrinology
Hong Xia, Xiangjun Huang, Yi Guo, Pengzhi Hu, Guangxiang He, Xiong Deng, Hongbo Xu, Zhijian Yang, Hao Deng
Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder, generally manifested with prelingual hearing loss and absence of other clinical manifestations. The aim of this study is to identify the pathogenic gene in a four-generation consanguineous Chinese family with ARNSHL. A novel homozygous variant, c.9316dupC (p.H3106Pfs*2), in the myoxin XVa gene (MYO15A) was identified by exome sequencing and Sanger sequencing. The homozygous MYO15A c.9316dupC variant co-segregated with the phenotypes in the ARNSHL family and was absent in two hundred normal controls...
2015: PloS One
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