Browsing by Subject "Carrier Proteins"

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Open Access
Aging alters the molecular dynamics of synapses in a sexually dimorphic pattern in zebrafish (Danio rerio)
(Elsevier, 2017-06) Karoglu, Elif Tugce; Halim, Dilara Ozge; Erkaya, Bahriye; Altaytas, Ferda; Arslan-Ergul, Ayca; Konu, Ozlen; Adams, Michelle M.
The zebrafish has become a popular model for studying normal brain aging due to its large fecundity, conserved genome, and available genetic tools; but little data exists about neurobiological age-related alterations. The current study tested the hypothesis of an association between brain aging and synaptic protein loss across males and females. Western blot analysis of synaptophysin (SYP), a presynaptic vesicle protein, and postsynaptic density-95 (PSD-95) and gephyrin (GEP), excitatory and inhibitory postsynaptic receptor-clustering proteins, respectively, was performed in young, middle-aged, and old male and female zebrafish (Danio rerio) brains. Univariate and multivariate analyses demonstrated that PSD-95 significantly increased in aged females and SYP significantly decreased in males, but GEP was stable. Thus, these key synaptic proteins vary across age in a sexually dimorphic manner, which has been observed in other species, and these consequences may represent selective vulnerabilities for aged males and females. These data expand our knowledge of normal aging in zebrafish, as well as further establish this model as an appropriate one for examining human brain aging.
Open Access
Coiled-Coil Domain Containing Protein 124 Is a Novel Centrosome and Midbody Protein That Interacts with the Ras-Guanine Nucleotide Exchange Factor 1B and Is Involved in Cytokinesis
(2013) Telkoparan P.; Erkek, S.; Yaman, E.; Alotaibi H.; Bayik, D.; Tazebay, U.H.
Cytokinetic abscission is the cellular process leading to physical separation of two postmitotic sister cells by severing the intercellular bridge. The most noticeable structural component of the intercellular bridge is a transient organelle termed as midbody, localized at a central region marking the site of abscission. Despite its major role in completion of cytokinesis, our understanding of spatiotemporal regulation of midbody assembly is limited. Here, we report the first characterization of coiled-coil domain-containing protein-124 (Ccdc124), a eukaryotic protein conserved from fungi-to-man, which we identified as a novel centrosomal and midbody protein. Knockdown of Ccdc124 in human HeLa cells leads to accumulation of enlarged and multinucleated cells; however, centrosome maturation was not affected. We found that Ccdc124 interacts with the Ras-guanine nucleotide exchange factor 1B (RasGEF1B), establishing a functional link between cytokinesis and activation of localized Rap2 signaling at the midbody. Our data indicate that Ccdc124 is a novel factor operating both for proper progression of late cytokinetic stages in eukaryotes, and for establishment of Rap2 signaling dependent cellular functions proximal to the abscission site. © 2013 Telkoparan et al.
Open Access
Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies
(Elsevier Ltd, 2014) Kayman-Kurekci G.; Talim, B.; Korkusuz P.; Sayar, N.; Sarioglu, T.; Oncel I.; Sharafi P.; Gundesli H.; Balci-Hayta, B.; Purali, N.; Serdaroglu-Oflazer P.; Topaloglu H.; Dincer P.
We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle. © 2014 Elsevier B.V.
Open Access
Regulation of Homer and group I metabotropic glutamate receptors by nicotine
(Wiley-Blackwell Publishing Ltd., 2005) Kane, J. K.; Hwang, Y.; Konu, O.; Loughlin, S. E.; Leslie, F. M.; Li, M. D.
The present study focuses on the nicotine-induced modulation of mRNA and protein expression of a number of genes involved in glutamatergic synaptic transmission in rat brain over different time periods of exposure. A subchronic (3 days) but not the chronic (7 or 14 days) administration of nicotine resulted in the up-regulation of Homer2a/b mRNA in the amygdala while in the ventral tegmental area (VTA) no change in expression of either Homer2a/b or Homer1b/c was observed. Although the increase in Homer2a/b mRNA was not translated into the protein level in the amygdala, a slight but significant up-regulation of Homer1b/c protein was observed in the same region at day 3. Both Homer forms were up-regulated at the protein level in the VTA at day 3. In the nucleus accumbens, 14 days of nicotine treatment up-regulated mRNA of Homer2b/c by 68.2% (P < 0.05), while the short form Homer1a gene was down-regulated by 65.0% at day 3 (P < 0.05). In regard to other components of the glutamatergic signalling, we identified an acute and intermittent increase in the mRNA and protein levels of mGluR1 and mGluR5 in the amygdala. In the VTA, however, the effects of nicotine on mGluR mRNA expression were long-lasting but rather specific to mGluR1. Nevertheless, mGluR1 protein levels in the VTA area were up-regulated only at day 3, as in the amygdala. These data provide further evidence for the involvement of nicotine in the glutamatergic neuronal synaptic activity in vivo, suggesting a role for the newly identified Homer proteins in this paradigm.