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Weng L.,Nagoya University | Enomoto A.,Nagoya University | Miyoshi H.,St. Marianna University School of Medicine | Takahashi K.,St. Marianna University School of Medicine | And 13 more authors.
EMBO Journal | Year: 2014

In clathrin-mediated endocytosis (CME), specificity and selectivity for cargoes are thought to be tightly regulated by cargo-specific adaptors for distinct cellular functions. Here, we show that the actin-binding protein girdin is a regulator of cargo-selective CME. Girdin interacts with dynamin 2, a GTPase that excises endocytic vesicles from the plasma membrane, and functions as its GTPase-activating protein. Interestingly, girdin depletion leads to the defect in clathrin-coated pit formation in the center of cells. Also, we find that girdin differentially interacts with some cargoes, which competitively prevents girdin from interacting with dynamin 2 and confers the cargo selectivity for CME. Therefore, girdin regulates transferrin and E-cadherin endocytosis in the center of cells and their subsequent polarized intracellular localization, but has no effect on integrin and epidermal growth factor receptor endocytosis that occurs at the cell periphery. Our results reveal that girdin regulates selective CME via a mechanism involving dynamin 2, but not by operating as a cargo-specific adaptor. Synopsis The actin binding protein girdin is a GAP for dynamin 2. Girdin regulates clathrin-dependent endocytosis through a non-canonical mechanism that involves competition between dynamin 2 and certain cargos for girdin binding, resulting in spatial control of protein internalization. The actin-binding protein girdin is a GAP for dynamin 2 involved in clathrin-dependent endocytosis. Girdin inhibits endocytosis of certain cargos but is required for others at the center but not the periphery of the cell. Competitive interaction between cargoes and dynamin 2 for girdin binding is involved in the selective endocytosis. The actin binding protein girdin is a GAP for dynamin 2. Girdin regulates clathrin-dependent endocytosis through a non-canonical mechanism that involves competition between dynamin 2 and certain cargos for girdin binding, resulting in spatial control of protein internalization. © 2014 The Authors. Source

Cui J.,Key Laboratory of Geriatrics | Cui J.,Chinese University of Hong Kong | Wu L.T.,Chinese University of Hong Kong | Wu L.T.,Northwestern University | Chu K.H.,Chinese University of Hong Kong
Molecular Biology Reports | Year: 2014

Two-dimensional electrophoresis and mass spectrometry were used to identify proteins that are differentially expressed during ovarian maturation in Metapenaeus ensis. 87 spots with consistently significant quantitative differences (≥1.5-fold for vol%) among stage I, III and V ovaries were chosen for MS/MS analysis. 45 spots were significantly matched to known proteins in the database (Mascot score >40). Half of them were down-regulated, in contrast to 9 out of 45 proteins that were up-regulated as ovarian maturation proceeded. Functionally, these identified proteins could be classified into five major groups, including cytoskeleton (11 %), metabolism (18 %), signal transduction (32 %), gene expression (14 %) and immune response (7 %). Among the differentially expressed reproduction-related proteins, the mRNA expression level of cellular retinoic acid/retinol binding protein in M. ensis (MeCRABP) during ovarian maturation was further characterized by quantitative real-time PCR. It was down-regulated during ovarian maturation. In situ hybridization further revealed that MeCRABP transcript was localized in ooplasm of previtellogenic oocytes but not in vitellogenic oocytes. These results demonstrate the application of proteomic analysis for identification of proteins involved in shrimp ovarian maturation and they provide new insights into ovarian development. © 2013 Springer Science+Business Media Dordrecht. Source

Shi F.,Peking Union Medical College | Shi F.,Key Laboratory of Geriatrics | Nie B.,Key Laboratory of Geriatrics | Nie B.,Wenzhou Medical College | And 7 more authors.
Free Radical Research | Year: 2012

The levels of the oxidised forms of guanosine in leukocytes, plasma and urine of Macaca mulatta were determined using a sensitive method based on high-performance liquid chromatographytriple quadruple mass spectrometry (LCMS/MS). The amounts of 8-oxo-7,8-dihydrodeoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosin (8-oxoGsn), derived from DNA and RNA, respectively, increased with age in leukocytes. The measurement of the free forms of oxidised guanosine revealed similar age-dependent increases of 8-oxo-dGsn and 8-oxoGsn in both plasma and urine, which showed considerably larger amounts of 8-oxoGsn than 8-oxo-dGsn. The 8-oxoGsn content of urine could be a useful biomarker for evaluating aging, as age-dependent increases of 8-oxoGsn are more evident in urine compared to plasma and because urine samples are readily available. © 2012 Informa UK, Ltd. Source

Liu M.,Peking Union Medical College | Wang J.,Beijing Hospital | Xu Y.,Tianjin Medical University | Wei D.,Beijing Hospital | And 2 more authors.
Journal of Urology | Year: 2012

Purpose: Genome-wide association studies have identified several genetic variants at 8q24 that are strongly associated with prostate cancer risk in populations of European, American and Japanese ancestry. We investigated the contribution of these prostate cancer risk variants in the Chinese population. Materials and Methods: We evaluated the association of 14 single nucleotide polymorphisms at 8q24 with prostate cancer risk using high resolution melting curve combined gene sequencing methods in case-control groups, including 265 cases and 288 controls. We explored the association between clinical covariates (age at diagnosis, prostate specific antigen, Gleason score and tumor stage) and risk loci in our study to infer their impact on aggressive prostate cancer. Results: Four of the 14 single nucleotide polymorphisms were associated with prostate cancer risk, including rs16901966 (OR 1.343, 95% CI 1.0291.754, p = 0.030), rs1447295 (OR 1.499, 95% CI 1.1092.027, p = 0.008), rs11986220 (OR 1.589, 95% CI 1.1602.178, p = 0.004) and rs10090154 (OR 1.571, 95% CI 1.1462.154, p = 0.005). Haplotype based association analysis of the risk alleles revealed significant differences between cases and controls. The risk alleles of rs16901966, rs1447295, rs11986220 and rs10090154 were associated with age at diagnosis and tumor stage compared with controls while rs16901966 was associated with aggressive prostate cancer (OR 1.538, 95% CI 1.0762.099, p = 0.018). Conclusions: For northern Chinese men rs16901966, rs1447295, rs11986220 and rs10090154 at 8q24 (region 1, region 2) are associated with prostate cancer and prostate cancer related clinical covariates. © 2012 American Urological Association Education and Research, Inc. Source

Shi X.,Key Laboratory of Geriatrics | Wang L.,CAS Institute of Genetics and Developmental Biology | Jin F.,CAS Institute of Psychology | Sun J.,Key Laboratory of Geriatrics | And 3 more authors.
Acta Diabetologica | Year: 2011

The K121Q polymorphism of the ectoenzyme nucleotide pyrophosphate phosphodiesterase 1 (ENPP1) gene has been studied in relation to insulin resistance, type 2 diabetes, and obesity, and conflicting results were observed in various populations. The purpose of the present study was to investigate the prevalence of K121Q polymorphism of ENPP1 gene and to clarify whether this polymorphism is associated with type 2 diabetes susceptibility in northern Chinese population. We studied the association of the ENPP1 K121Q polymorphism with type 2 diabetes (T2D) in 639 unrelated patients and 885 control subjects with normal glucose tolerance of northern China. The patients were diagnosed in accordance with the guidelines of the American Diabetes Association (ADA). Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The distribution of KK, KQ, and QQ genotypes among patients was 79.5, 19.2, and 1.3%, similar to that of the control group (79.2, 20.1, and 0.7%). After readjusting for the confounding effects of age, gender, and BMI, no significant effect of genotypes on T2D was found for any of the genetic models tested (recessive model, dominant model, or additive model). All clinical characteristics tested were similar among the different genotypes, and no significant associations were observed both in T2D patients and in controls. When subgroup analyses of T2D patients and non-diabetic controls were stratified according to BMI and waist circumference, the variant was still not associated with T2D. The results showed that the ENPP1 K121Q polymorphism is not associated with genetic susceptibility of type 2 diabetes in the northern Chinese population. © 2011 Springer-Verlag. Source

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