A novel early estrogen-regulated gene gec1 encodes a protein related to GABARAP

Institut d'Etude et de Transfert de Gènes, Bâtiment INSERM, Besançon, France.
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 07/2001; 284(1):118-25. DOI: 10.1006/bbrc.2001.4908
Source: PubMed


We have isolated, in guinea-pig endometrial cells, an estrogen-induced 1.8 kb RNA called gec1. Screening of a guinea-pig genomic library led to identification of gec1 gene consisting of 4 exons and 3 introns. Exon 1 contains the 5'UTR and the ATG initiation codon. A guinea-pig gec1 cDNA was obtained by 5'-RACE. The 351 bp coding sequence shares 76.8% identity with that of the human GABARAP 924 bp cDNA while UTRs of the two cDNAs differ. A gec1 probe from the 3'UTR revealed a 1.9 kb mRNA in human tissues and a human GEC1 cDNA was isolated from placenta. Its coding sequence shares 93 and 79% identity with that of guinea-pig gec1 and human GABARAP, respectively. The human and guinea-pig GEC1 proteins have 100% identity. GEC1 and GABARAP proteins have 87% identity and N terminus featuring a tubulin binding motif. Thus, estrogen-regulated gec1 is a new gene which could encode a microtubule-associated protein.

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    • "GABARAPL1 may, therefore, play a protective role in this disease by aiding in the degradation of unwanted α-synuclein aggregates until such time as it is downregulated with the progression of the disease. Indeed, gabarapl1 transcription is upregulated in the presence of estrogens [42] and estrogen has been show to have a protective effect on an MPTP murine model of Parkinson's disease [43]. "
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    ABSTRACT: Macroautophagy is a highly conserved cellular degradation process, regulated by autophagy-related (atg) factors, in which a double membrane autophagosome engulfs cytoplasmic components to target them for degradation. In yeast, the Atg8 protein is indispensable for autophagosome formation. In mammals, this is complicated by the presence of six Atg8 homologues grouped into the GABARAP and MAP1LC3 subfamilies. Although these proteins share a high similarity, their transcript expression, regulation and protein interactions differ, suggesting they may display individual properties and specific functions. GABARAPL1/GEC1 is a member of the GABARAP subfamily and its mRNA is the most highly expressed Atg8 homologue in the central nervous system. Consequently, we performed an in depth study of GABARAPL1 distribution in the developing and adult murine brain. Our results show that GABARAPL1 brain expression is visible as early as embryonic day 11 and progressively increases to a maximum level in the adult. Immunohistochemical staining was detected in both fibers and immature neurons in embryos but was restrained to neurons in adult tissue. By E17, intense punctate-like structures were visible and these accumulated in cortical primary neurons treated with the autophagosome/lysosome fusion inhibitor Bafilomycin A1 (Baf A1), suggesting that they represent autophagosomes. Finally, GABARAPL1 expression was particularly intense in motoneurons in the embryo and in neurons involved in somatomotor and neuroendocrine functions in the adult, particularly in the substantia nigra pars compacta, a region affected in Parkinson's disease. Our study of cerebral GABARAPL1 protein expression provides insight into its role in the development and homeostasis of the mouse brain.
    PLoS ONE 05/2013; 8(5):e63133. DOI:10.1371/journal.pone.0063133 · 3.23 Impact Factor
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    • "GABARAP has also been characterized as a mammalian homolog of the yeast Atg8 (autophagy-related protein8)/Apg8/Aut7; other homologues include LC3 (microtubule-associated protein 1 light chain 3), Golgi-associated ATPase enhancer of 16 kDa (GATE-16)/GABARAPL2/GEF2, and Atg8L [10], [11]. GABARAP is also highly homologous with the other Atg8 homologs, especially with Atg8L/GEC1/GABARAPL1 (87% identity and 97% similarity) and GATE-16 (57% identity and 97% similarity) [4], [12], [13], [14], [15], [16]. We have shown that GABARAP, along with the other Atg8 homologs, can act as a ubiquitin-like modifier protein, and that GABARAP modification is mediated by the cysteine protease Atg4B, the E1-like enzyme Atg7/Apg7, and the E2-like enzyme Atg3/Apg3 [10], [11], [17], [18], [19], [20]. "
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    ABSTRACT: GABAA receptor-associated protein (GABARAP) was initially identified as a protein that interacts with GABAA receptor. Although LC3 (microtubule-associated protein 1 light chain 3), a GABARAP homolog, has been localized in the dendrites and cell bodies of neurons under normal conditions, the subcellular distribution of GABARAP in neurons remains unclear. Subcellular fractionation indicated that endogenous GABARAP was localized to the microsome-enriched and synaptic vesicle-enriched fractions of mouse brain as GABARAP-I, an unlipidated form. To investigate the distribution of GABARAP in neurons, we generated GFP-GABARAP transgenic mice. Immunohistochemistry in these transgenic mice showed that positive signals for GFP-GABARAP were widely distributed in neurons in various brain regions, including the hippocampus and cerebellum. Interestingly, intense diffuse and/or fibrillary expression of GFP-GABARAP was detected along the axonal initial segments (AIS) of hippocampal pyramidal neurons and cerebellar Purkinje cells, in addition to the cell bodies and dendrites of these neurons. In contrast, only slight amounts of LC3 were detected along the AIS of these neurons, while diffuse and/or fibrillary staining for LC3 was mainly detected in their cell bodies and dendrites. These results indicated that, compared with LC3, GABARAP is enriched in the AIS, in addition to the cell bodies and dendrites, of these hippocampal pyramidal neurons and cerebellar Purkinje cells.
    PLoS ONE 05/2013; 8(5):e63568. DOI:10.1371/journal.pone.0063568 · 3.23 Impact Factor
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    • "a metallic template leading to a highly controlled monolayer of macromolecular species (Park and Kim, 1998). In our laboratory, we have recently identified a novel gene called GEC1 (Vernier-Magnin et al., 2001). GEC1 has been shown to associate with tubulin and microtubules and may be involved in GABA A receptor trafficking in synapses along the cytoskeleton (Mansuy et al., 2004; Wang and Olsen, 2000; Wang et al., 1999). "
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    ABSTRACT: Many biotechnology applications use proteins immobilized on surface. For biosensor, the sensing layer is a key component interfacing the transducer and the sample. Strategies employed to activate the bidimensional surface act directly on the performance of the biosensor. In this paper we propose a novel strategy for engineered proteins self-assembly. Our original supramolecular structure allows a direct and fast covalent attachment of proteins onto bare gold substrate through a homobifunctional cross-linker, 1,4-di-([2'-pyridyldithio]propionamido)butane (DPDPB). In this work, engineered proteins and linker-protein complexes were synthesized and characterized by gel electrophoresis, chromatography and spectroscopy experiments. Macromolecular construction "DPDPB-GST tag-GEC1 protein" was conceived in order to guarantee a 2D architecture enhancing the capabilities of the target (tubulin) to recognize its partner (GEC1). Surface plasmon resonance measurements clearly showed potential of this particular self-assembled protein layer compared to a commercial immunosensor interface. At the concentrations tested, the recognition process occurs between tubulin and the immobilized GEC1; moreover enhanced binding was obtained with the home-made 2D sensing layer more than with 3D carboxymethyl dextran matrix.
    Biosensors & Bioelectronics 04/2006; 21(9):1830-7. DOI:10.1016/j.bios.2005.11.021 · 6.41 Impact Factor
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