Specific distribution of gabarap, gec1/gabarap Like 1, gate16/gabarap Like 2, lc3 messenger RNAs in rat brain areas by quantitative real-time PCR
Université de Franche-Comté, IFR 133, U.F.R. Sciences et Techniques, Equipe Estrogènes, Expression Génique et Pathologies du Système Nerveux Central, 16 route de Gray, 25030 Besançon cedex, France. Brain Research
(Impact Factor: 2.84).
03/2006; 1073-1074(1):83-7. DOI: 10.1016/j.brainres.2005.11.004
GABARAP and GEC1/GABARAPL1 interact with tubulin and GABA(A) receptor and belong to a new protein family. This family includes GATE 16 and LC3, potentially involved in intracellular transport processes. In this study, we combined brain dissection and quantitative real-time reverse transcription polymerase chain reaction to study discriminatively gabarap, gec1/gabarapL1, gate16/gabarapL2, lc3 mRNA distribution in multiple rat brain areas.
Available from: Gen Kaneko
- "Since its discovery, GABARAP and its orthologs have been found in almost all organisms as diverse from yeast to human. Human GABARAPs, which are linker proteins between microtubules and g subunit of GABA A receptors are expressed ubiquitously in the central nervous system, and a few in endocrine organs and other tissues  . Amphioxus GABARAPs are expressed ubiquitously, with the highest expression in the enteric nervous system, notochord, and ovary, although its precise function is unknown  . "
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ABSTRACT: γ-Aminobutyric acid receptor type A-associated protein (GABARAP) and its homologs constitute a protein family found in many eukaryotes from yeast to human, and are known to be involved in intracellular membrane trafficking of GABAA receptors and autophagy. In this study, we cloned cDNA-encoding GABARAP from the monogonont rotifer Brachionus plicatilis and examined for its tissue distribution at the protein level in neonates, males and females. Using reverse transcription (RT)-PCR and rapid amplification of cDNA ends (RACE) techniques, we showed that like other GABARAPs, rotifer GABARAP was also composed of 117 amino acids and highly homologous to vertebrate GABARAP2 ortholog (74–76% identity). GABARAP was demonstrated with its specific antibody to be ubiquitously distributed, irrespective of neonates, males, and females, in the coronal area that covers brain and contains most mechano- and chemoreceptors. Rotifer GABARAP was also expressed in the mature eggs but not in immature eggs. Double immunostaining with mammalian anti-GABA γ receptor antibody showed that rotifer GABARAP co-localized with GABA receptor, suggesting the association of the two proteins. The presence of GABARAP in rotifer implies that it is highly conserved during evolution, and plays important roles in various biological processes.
Available from: Jianhua Zhang
- "To date, no other mammalian Atg8 protein homologue has been mapped out in the adult brain, although their mRNA expression levels have been observed , . As such, protein mapping of the other members of the GABARAP and LC3 families in the brain would be very interesting in order to determine if there is a compensation of the other members in the cells in which GABARAPL1 is less strongly expressed. "
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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.
Available from: jneurosci.org
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ABSTRACT: Fast inhibitory synaptic transmission is predominantly mediated by GABA(A) receptor (GABA(A)R) in the CNS. Although several types of neuronal activity-dependent plasticity at GABAergic synapses have been reported, the detailed mechanism is elusive. Here we show that binding of structurally altered GABA(A)R-associated protein (GABARAP) to GABA(A)R gamma2 subunit and to tubulin is critical for long-term potentiation [called rebound potentiation (RP)] at inhibitory synapses on a cerebellar Purkinje neuron (PN). Either inhibition of GABARAP association with GABA(A)Rgamma2 or deletion of tubulin binding region of GABARAP impaired RP. Inhibition of tubulin polymerization also suppressed RP. Thus, precise regulation of GABA(A)Rgamma2-GABARAP-microtubule interaction is critical for RP. Furthermore, competitive inhibition of GABARAP binding to GABA(A)Rgamma2 after the RP establishment attenuated the potentiated response, suggesting that GABARAP is critical not only for the induction but also for the maintenance of RP. Fluorescence resonance energy transfer analysis revealed that GABARAP underwent sustained structural alteration after brief depolarization of a PN depending on the activity of Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is required for the RP induction. The susceptibility of GABARAP to undergo structural alteration was abolished by an amino acid replacement in GABARAP. Furthermore, RP was impaired by expression of the mutant GABARAP with the replacement. Together, we conclude that GABA(A)R association with structurally altered GABARAP downstream of CaMKII activation is essential for RP.
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