Gamma-aminobutyric acid receptor subunit delta is a protein that in humans is encoded by the GABRDgene.[5][6][7] In the mammalian brain, the delta (δ) subunit forms specific GABAA receptor subtypes by co-assembly leading to δ subunit containing GABAA receptors (δ-GABAA receptors).[8]
Function
The delta (δ) subunit, one of the subunits of the hetero-pentameric δ-GABAA receptors, is a determinant subunit for the specific cellular localization of δ-GABAA receptors,[8][9] which are modulated by the GABA. GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts on the repertoire of GABAA receptors, the ligand-gated chloride channels. It is assembled from a diverse subunit pool, including assemblies from a family of 19 subunits (α1-α6, β1-β3, γ1-γ3, δ, ∈, θ, π and ρ1-ρ3).[10][9] The GABRD gene encodes the delta (δ) subunit.[7] Specifically, the δ-subunit is usually expressed in GABAA receptors associated with extrasynaptic activity, mediating tonic inhibition, which is slower compared to classical inhibition (phasic or synaptic inhibition).[9] The most common GABAA receptors have the gamma subunit, which allows the receptor to bind benzodiazepines. For this reason, receptors containing δ-subunits (δ-GABAA receptor) are sometimes referred to as “benzodiazepine-insensitive” GABAA receptors. However, they do show an exquisitely high sensitivity to ethanol compared to the benzodiazepine-sensitive receptors, which do not respond to ethanol however these results are not fully confirmed in the literature.[8] The δ-subunit containing receptors are also known to be involved in the ventral tegmental area (VTA) pathway in the brain's hippocampus, which means that they may have implications in learning, memory, and reward.[11]
Clinical significance
Neurological and psychiatric disorders
Mutations or dysregulation of GABRD and other GABA-A receptor subunits have been implicated in conditions such as epilepsy, anxiety disorders, and certain neurodevelopmental disorders.[12][13]
Research has suggested that alterations in the GABRD gene may be linked to certain neurological and psychiatric disorders, including anxiety. Anxiety disorders are a group of mental health conditions characterized by excessive and persistent worry, fear, or nervousness. The GABA system, including the GABRD gene, is implicated in the regulation of anxiety and stress responses. While there is ongoing research to understand the complex genetic and neurobiological factors contributing to anxiety disorders, it's important to note that anxiety is a multifaceted condition influenced by a combination of genetic, environmental, and psychological factors. Many genes, neurotransmitters, and brain regions are likely involved in the development and manifestation of anxiety. Individuals with variations in the GABRD gene may exhibit differences in GABA-A receptor function, which could potentially influence their susceptibility to anxiety or other related conditions. However, the interplay of genetics with environmental factors is complex, and it's crucial to consider a holistic perspective when understanding the causes of anxiety.[14]
Epilepsy is a neurological disorder characterized by recurrent, unprovoked seizures. GABAergic neurotransmission, mediated by the GABA-A receptor, is essential for maintaining the balance between excitatory and inhibitory signals in the brain. Changes in the functioning of GABA receptors, including those associated with the GABRD gene, can influence this balance and potentially contribute to the development of epilepsy. Research has suggested that alterations in the GABRD gene may be implicated in certain forms of epilepsy. Mutations or variations in genes encoding GABA receptor subunits can affect the function of these receptors, leading to an imbalance in excitatory and inhibitory neurotransmission, which may contribute to the hyperexcitability observed in epilepsy. It's important to note that epilepsy is a complex disorder with various genetic and environmental factors contributing to its development. While some individuals with epilepsy may have genetic mutations affecting GABA receptors, not all cases are directly linked to specific genes.[15]
GABA levels, known as the neurotransmitter, one of the most important signals of the mammalian brain, have recently been involved in mood disorders. Genetic studies have also shown that some genes are involved in mood disorders. GABARD is one of the strong candidates among these genes. As a result of studies, it has been proven that the 8 subunits encoded by GABRD are linked to major depressive disorders.[16]
Cancer
GABRD effect has also been observed in some types of cancer. For example, GABRD effect has been observed in colorectal cancer. According to research conducted by scientists, it has been observed that colorectal cancers metastasize.[17] In some neurological diseases, some mutations occur depending on GABRD gene expression, and as a result of these mutations, some diseases occur, for example, epilepsy. Epilepsy is called the sudden discharge process that occurs in the brain, and as a result, sudden contractions occur in the body. but the role of GABRD in epilepsy is less. It has also been observed that it has an effect on autism spectrum disorder as a result of the variation of the GABRD protein.[18] The GABRD gene encodes the δ subunit of the GABA A receptor, which is highly expressed in the brain and mediates tonic inhibition-related signaling. It has also been proven that excessive release of neurotransmitters plays a role in triggering some types of cancer and uncontrolled cell proliferation. In recent studies, GABRD gene expression is at very high levels in colon adenocarcinoma. In addition, scientists have proven in their research that Gabrd expression is excessive in the relevant tissues.[19]
Tissue distribution
The cellular localization of mRNAs of 13 GABAA receptor subunits was analyzed in different brain regions.[20] For example, in the cerebellum, various receptor subtypes are found in cerebellar granule cells and Purkinje cells, whereas in the olfactory bulb, periglomerular cells, tufted cells, and internal granule cells express GABAA receptor subtypes.[21] Specifically, the pattern of cell type-specific δ subunit expression is shown in the table below.
Cell type-specific expression of δ subunit and its co-assembly[8]
The GABRD gene, encoding the delta subunit of the GABAA receptor, exhibits cell type-specific expression patterns. Primarily found in neurons, particularly in brain regions like the hippocampus and cerebral cortex, GABRD plays a crucial role in inhibitory neurotransmission. Its expression dynamically changes during development, influencing synaptic maturation. Emerging evidence suggests GABRD expression in certain glial cells, indicating potential roles in glia-neuron communication. Additionally, GABRD is detected in peripheral tissues, hinting at non-neuronal functions. Altered GABRD expression is linked to neurological disorders, emphasizing its significance.[24]
Cloning
GABAA receptors were initially cloned by the classical method that the peptide sequences obtained from purified (bovine brain) receptors were used to construct synthetic DNA probes to screen brain cDNA libraries.[9][25][26] Eventually, this technique have led to the identification of most of the gene family with its isoforms: α1-α6, β1-β3, γ1-γ3 subunits and one δ subunit.[27]
GFP tagging
Subunits of GABA A receptors were tagged by Green Fluorescent Protein (GFP) or its variants (EGFP) to study trafficking, localization, oligomerization, and protein interactions of relevant receptor subtypes and the relevant subunits. Typically, the EGFP or GFP tagging has been done in the N-terminus or C-terminus of the mature peptide sequence of relevant subunit. The GFP tagging of δ-subunit was performed in the different domains of the subunit such as the N-terminus, C-terminus as well as intracellular (cytoplasmic) domain.[28][29][30] Nevertheless, despite these and other studies, it is not clear if this subunit requires α and β subunits for the membrane targeting since literature suggests conflicting results. By the use of GFP tagging of this subunit, one group reported that the cell membrane expression of the δ subunit was observed only in the presence of both α and β subunits.[30] However, another group suggested that the δ subunit can target to the cell membrane and the βδ containing receptors exist.[31]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Sommer B, Poustka A, Spurr NK, Seeburg PH (October 1990). "The murine GABAA receptor delta-subunit gene: structure and assignment to human chromosome 1". DNA and Cell Biology. 9 (8): 561–568. doi:10.1089/dna.1990.9.561. PMID2176788.
^Emberger W, Windpassinger C, Petek E, Kroisel PM, Wagner K (Sep 2000). "Assignment of the human GABAA receptor delta-subunit gene (GABRD) to chromosome band 1p36.3 distal to marker NIB1364 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 89 (3–4): 281–282. doi:10.1159/000015636 (inactive 2024-07-16). PMID10965146. S2CID83974022.{{cite journal}}: CS1 maint: DOI inactive as of July 2024 (link)
^ abcdGoetz T, Arslan A, Wisden W, Wulff P (2007). "GABAA receptors: Structure and function in the basal ganglia". GABA(A) receptors: structure and function in the basal ganglia. Progress in Brain Research. Vol. 160. Elsevier. pp. 21–41. doi:10.1016/s0079-6123(06)60003-4. ISBN978-0-444-52184-2. PMC2648504. PMID17499107.
^Dibbens LM, Feng HJ, Richards MC, Harkin LA, Hodgson BL, Scott D, et al. (July 2004). "GABRD encoding a protein for extra- or peri-synaptic GABAA receptors is a susceptibility locus for generalized epilepsies". Human Molecular Genetics. 13 (13): 1315–1319. doi:10.1093/hmg/ddh146. PMID15115768.
^Bhat MA, Guru SA, Mir R, Waza AA, Zuberi M, Sumi MP, et al. (June 2018). "Association of GABAA Receptor Gene with Epilepsy Syndromes". Journal of Molecular Neuroscience. 65 (2): 141–153. doi:10.1007/s12031-018-1081-7. PMID29785705. S2CID29167453.
^Schofield PR, Darlison MG, Fujita N, Burt DR, Stephenson FA, Rodriguez H, et al. (July 1987). "Sequence and functional expression of the GABA A receptor shows a ligand-gated receptor super-family". Nature. 328 (6127): 221–227. Bibcode:1987Natur.328..221S. doi:10.1038/328221a0. PMID3037384. S2CID4242202.
^Seeburg PH, Wisden W, Verdoorn TA, Pritchett DB, Werner P, Herb A, et al. (1990-01-01). "The GABAA receptor family: molecular and functional diversity". Cold Spring Harbor Symposia on Quantitative Biology. 55: 29–40. doi:10.1101/SQB.1990.055.01.006. PMID1966765.
^Arslan A, von Engelhardt J, Wisden W (December 2014). "Cytoplasmic domain of δ subunit is important for the extra-synaptic targeting of GABAA receptor subtypes". Journal of Integrative Neuroscience. 13 (4): 617–631. doi:10.1142/S0219635214500228. PMID25233879.
^Christie SB, Li RW, Miralles CP, Yang B, De Blas AL (January 2006). "Clustered and non-clustered GABAA receptors in cultured hippocampal neurons". Molecular and Cellular Neurosciences. 31 (1): 1–14. doi:10.1016/j.mcn.2005.08.014. PMID16181787. S2CID40720887.
^Lee HJ, Absalom NL, Hanrahan JR, van Nieuwenhuijzen P, Ahring PK, Chebib M (August 2016). "A pharmacological characterization of GABA, THIP and DS2 at binary α4β3 and β3δ receptors: GABA activates β3δ receptors via the β3(+)δ(-) interface". Brain Research. 1644: 222–230. doi:10.1016/j.brainres.2016.05.019. PMID27181518. S2CID206337032.
Lenzen KP, Heils A, Lorenz S, Hempelmann A, Sander T (June 2005). "Association analysis of the Arg220His variation of the human gene encoding the GABA delta subunit with idiopathic generalized epilepsy". Epilepsy Research. 65 (1–2): 53–57. doi:10.1016/j.eplepsyres.2005.04.005. PMID16023832. S2CID20661316.
Windpassinger C, Kroisel PM, Wagner K, Petek E (June 2002). "The human gamma-aminobutyric acid A receptor delta (GABRD) gene: molecular characterisation and tissue-specific expression". Gene. 292 (1–2): 25–31. doi:10.1016/S0378-1119(02)00649-2. PMID12119096.
1886 Kansas City CowboysLeagueNational LeagueBallparkAssociation ParkCityKansas City, MissouriManagerDave Rowe The 1886 Kansas City Cowboys was a season in American baseball. The team had a 30–91 record in the National League, finishing in seventh place. This was the only season this version of the team existed, as the team went bankrupt before the 1887 season. Regular season Season standings vteNational League W L Pct. GB Home Road Chicago White Stockings 90 34 0.726 — 52–10 38–...
Força Aérea da Lituânia País Lituânia Efectivo ~ 1 000 militares14 aeronaves Bases Aéreas Bases Aéreas Base aérea de Siauliai Aeronaves Aviões de Ataque L-39ZA Helicópteros Mi-8MTV-1, Mi-8T, Mi-8PS, AS365 Aviões de Transporte C-27J, L-410 Insígnias Cocar Bandiera Comando Comandante-em-chefe Brigadeiro-general Antanas Gustaitis Comandante Coronel Audronis Navickas Sede Quartel-general Kaunas A Força Aérea da Lituânia é o ramo aéreo das Forças Armadas da Lituânia. A sua...
Johanna SpyriBiographieNaissance 12 juin 1827HirzelDécès 7 juillet 1901 (à 74 ans)ZurichSépulture Cimetière de Sihlfeld (d)Nationalité suisseActivités Écrivaine, romancière, autrice de littérature pour la jeunessePère Johann Jakob Heusser (d)Mère Meta Heusser-Schweizer (d)Conjoint Johann Bernhard Spyri (d)Parentèle Émilie Kempin-Spyri (nièce)Œuvres principales HeidiVue de la sépulture.modifier - modifier le code - modifier Wikidata Johanna Spyri (née Johanna Heusse...
Untuk kapal lain dengan nama serupa, lihat Kapal perusak Jepang Uranami. Uranami mengarungi lautan pada September 1931 Sejarah Kekaisaran Jepang Nama UranamiAsal nama Kapal perusak Jepang Uranami (1907)Dipesan 1923 (Tahun Fiskal)Pembangun Uraga Dock CompanyPasang lunas 28 April 1927 sebagai Perusak No.44Diluncurkan 29 November 1928Mulai berlayar 30 Juni 1929Identifikasi Nomor lambung: 19Nasib Tenggelam pada 26 Oktober 1944 Ciri-ciri umum Kelas dan jenis Kapal perusak kelas-FubukiBer...
هذه المقالة يتيمة إذ تصل إليها مقالات أخرى قليلة جدًا. فضلًا، ساعد بإضافة وصلة إليها في مقالات متعلقة بها. (أكتوبر 2019) يعني العائد الديموغرافي بحسب تعريف صندوق الأمم المتحدة للسكان، «نمو اقتصادي محتمل يمكن أن ينشأ عن تحولات في التركيبة العمرية للسكان، وذلك بالأساس عندما تكو
Kia SorentoInformasiProdusenKia MotorsMasa produksi2002–sekarangBodi & rangkaKelas Compact SUV (2002–2009) Mid-size crossover SUV (2009–present) Bentuk kerangka5-door SUVKronologiPendahuluKia Borrego (North America)Kia Sorento adalah sebuah SUV crossover menengah (SUV kompak sampai dengan 2009) diproduksi sejak 2002 oleh perusahaan mobil Korea Selatan Kia Motors. Generasi Pertama (2002–2009) 2002–2009 First generation (BL)InformasiJuga disebutNaza Sorento (Malaysia)Pye...
Representative of the British monarch in Guernsey Lieutenant Governor of GuernseyCoat of arms of GuernseyFlag of the lieutenant governor of GuernseyIncumbentLieutenant General Richard Cripwell CB CBEsince 15 February 2022StyleHis ExcellencyAppointerMonarch of the United KingdomTerm lengthAt His Majesty's PleasureWebsitewww.governmenthouse.gg Politics of Guernsey The Crown Duke of Normandy King Charles III Lieutenant Governor Vice Admiral Ian Corder KBE, CB Government President of the...
Japanese actress, former member of AKB48, member of no3b (1988-) Haruna Kojima小嶋 陽菜Born (1988-04-19) April 19, 1988 (age 35)Urawa-ku, Saitama, Saitama Prefecture, JapanOccupations Actress singer model entrepreneur Years active1998–2001, 2005–presentHeight164 cm (5 ft 5 in)Musical careerGenresJ-popInstrument(s)VocalsLabels King (AKB48) Epic (no3b) Musical artistYouTube informationChannel Haruna Kojima's Cat Nap Years active2019–presentGenres Beauty v...
Battleship of the German Imperial Navy Kaiser Karl der Grosse in 1902 History German Empire NameKaiser Karl der Grosse NamesakeCharlemagne (Karl der Grosse in German) BuilderBlohm & Voss, Hamburg Laid down17 September 1898 Launched18 October 1899 Commissioned4 February 1902 Decommissioned19 November 1915 Stricken6 December 1919 FateScrapped in 1920 General characteristics Class and typeKaiser Friedrich III-class pre-dreadnought battleship Displacement Normal: 11,097 t (10,922 long to...
1988 studio album by Foetus InterruptusThawStudio album by Foetus InterruptusReleasedSeptember 1988RecordedDecember 1987 (1987-12)–March 1988 (1988-03) at BC Studio, Brooklyn, New YorkGenreIndustrialLength39:34LabelSelf Immolation/Some BizzareProducerJ. G. ThirlwellJ. G. Thirlwell chronology Stinkfist(1987) Thaw(1988) Rife(1988) Professional ratingsReview scoresSourceRatingAllMusic[1]NME[2]Sounds[3] Thaw is a Foetus Interruptus album relea...
August MöbiusAugust Ferdinand Möbius (1790–1868)LahirAugust Ferdinand Möbius(1790-11-17)17 November 1790Schulpforta, Elektorat SaxonyMeninggal26 September 1868(1868-09-26) (umur 77)Leipzig, Konfederasi JermanTempat tinggalJermanKebangsaanSaxonAlmamaterUniversitas LeipzigUniversitas GöttingenUniversitas HalleKarier ilmiahBidangMatematikawanInstitusiUniversitas LeipzigPembimbing doktoralJohann PfaffPembimbing akademik lainCarl Friedrich GaussKarl MollweideMahasiswa doktoralOtto ...
Railway station in West Bengal, India This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages) This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed.Find sources: Daulatpur railway station – news · newspapers · books · scholar · JST...
18th-century British gentlewoman Dido Elizabeth BellePainting of Belle (cropped), David MartinBornJune 1761 (1761-06)British West IndiesDiedJuly 1804 (aged 42–43)London, EnglandResting placeSt George's Fields, Westminster (1804–1970s)NationalityBritishSpouse Jean Louis Charles Davinière (m. 1793)Children3Parents Sir John Lindsay Maria Belle Relatives Sir Alexander Lindsay, 3rd Baronet (grandfather) William Murray, 1st Earl of Mansfield...
English nautical captain For Sir Bernard Drake, 3rd Baronet (died 1687), see Drake baronets. Not to be confused with Bernard Darke. Monumental brass in Filleigh Church, North Devon, depicting Sir Bernard Drake (d. 1586), who erected the monument to which it was originally affixed in memory of his brother-in-law, Richard Fortescue (d. 1570). Arms of Drake of Ash: Argent, a wyvern wings displayed and tail nowed gules Ash, ancient seat of the Drakes, watercolour dated 13 February 1795 by Rev. Jo...
Pembagian dari Frekuensi radio : Frekuensi amat rendah - Frekuensi super rendah - Frekuensi ultra rendah - Frekuensi sangat rendah - Frekuensi rendah - Frekuensi sedang - Frekuensi tinggi - Frekuensi sangat tinggi - Frekuensi ultra tinggi - Frekuensi super tinggi - Frekuensi amat tinggi Pita radio ITU 1 (ELF) 2 (SLF) 3 (ULF) 4 (VLF) 5 (LF) 6 (MF) 7 (HF) 8 (VHF) 9 (UHF) 10 (SHF) 11 (EHF) 12 (THF) EU / NATO / US ECM A B C D E F G H I J K L M N IEEE HF VHF UHF L S C X Ku K Ka V W ...
Prague metro station For other uses, see Florence (disambiguation). FlorencPrague MetroLine C platformGeneral informationLocationSokolovskáPrague 8 - KarlínPragueCzech RepublicCoordinates50°05′28″N 14°26′20″E / 50.091°N 14.439°E / 50.091; 14.439Owned byDopravní podnik hl. m. PrahyLine(s)B CPlatforms2 island platformsTracks4ConstructionStructure typeUndergroundPlatform levels2ParkingNoBicycle facilitiesNoAccessibleYes (both stations)Other informationFare ...
Trade union of Liechtenstein LANVLiechtenstein Employees' AssociationLiechtensteiner ArbeitnehmerInnenverbandFounded1920HeadquartersTriesen, LiechtensteinMembers 1300Key peopleSigi Langenbahn, presidentAffiliationsITUC, ETUCWebsitewww.lanv.li The Liechtenstein Employees' Association (LANV) is the only trade union in Liechtenstein. It was founded in 1920 and is affiliated with the International Trade Union Confederation.[1] References ^ Platz, Dorothee (31 December 2011). Liechtenstein...
موكب الحبThe Love Paradeمعلومات عامةالصنف الفني كوميديتاريخ الصدور 1929مدة العرض 107 دقيقةاللغة الأصلية الإنجليزيةالعرض أبيض وأسود البلد الولايات المتحدةالطاقمالمخرج إرنست لوبيتش[1] السيناريو قاي بولتون — Ernest Vajda (en) البطولة القائمة ... موريس شيفالييه[2] جانيت ماكدون...