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Hetero-oligomerization between GABAA and GABAB receptors regulates GABAB receptor trafficking 总被引:4,自引:0,他引:4
Balasubramanian S Teissére JA Raju DV Hall RA 《The Journal of biological chemistry》2004,279(18):18840-18850
The neurotransmitter gamma-aminobutyric acid (GABA) mediates inhibitory signaling in the brain via stimulation of both GABA(A) receptors (GABA(A)R), which are chloride-permeant ion channels, and GABA(B) receptors (GABA(B)R), which signal through coupling to G proteins. Here we report physical interactions between these two different classes of GABA receptor. Association of the GABA(B) receptor 1 (GABA(B)R1) with the GABA(A) receptor gamma2S subunit robustly promotes cell surface expression of GABA(B)R1 in the absence of GABA(B)R2, a closely related GABA(B) receptor that is usually required for efficient trafficking of GABA(B)R1 to the cell surface. The GABA(B)R1/gamma2S complex is not detectably functional when expressed alone, as assessed in both ERK activation assays and physiological analyses in oocytes. However, the gamma2S subunit associates not only with GABA(B)R1 alone but also with the functional GABA(B)R1/GABA(B)R2 heterodimer to markedly enhance GABA(B) receptor internalization in response to agonist stimulation. These findings reveal that the GABA(B)R1/gamma2S interaction results in the regulation of multiple aspects of GABA(B) receptor trafficking, allowing for cross-talk between these two distinct classes of GABA receptor. 相似文献
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Single nucleotide RNA choreography 总被引:1,自引:1,他引:0
New structural analysis methods, and a tree formalism re-define and expand the RNA motif concept, unifying what previously appeared to be disparate groups of structures. We find RNA tetraloops at high frequencies, in new contexts, with unexpected lengths, and in novel topologies. The results, with broad implications for RNA structure in general, show that even at this most elementary level of organization, RNA tolerates astounding variation in conformation, length, sequence and context. However the variation is not random; it is well-described by four distinct modes, which are 3-2 switches (backbone topology variations), insertions, deletions and strand clips. 相似文献
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Proteasome is a major protease of the ubiquitin-proteasome pathway involved in the regulation of practically all intracellular biochemical processes. The enzyme core is created by a heteromultimer of complex architecture built with multiple subunits arranged into a tube-like structure. The multiple active sites of diverse peptidase specificity are hidden inside the tube. Access to the interior is guarded by a gate formed by the N-termini of specialized subunits and by the attachment of additional multisubunit protein complexes controlling the enzymatic capabilities of the core. Proteasome, due to its Byzantine molecular architecture and equally sophisticated enzymatic mechanism, is by itself a fascinating biophysical object. Recently, the position of the protease advanced from an academically remarkable protein processor to a providential anticancer drug target and futuristic nanomachine. Proteomics studies actively shape our current understanding of the protease and direct the future applications of the proteasome in medicine. 相似文献
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Subramanian Swaminathan Vanamail Perumal Srividya Adinarayanan Krishnamoorthy Kaliannagounder Ravi Rengachari Jambulingam Purushothaman 《PLoS neglected tropical diseases》2012,6(11)
Background
Monitoring and evaluation guidelines of the programme to eliminate lymphatic filariasis require impact assessments in at least one sentinel and one spot-check site in each implementation unit (IU). Transmission assessment surveys (TAS) that assess antigenaemia (Ag) in children in IUs that have completed at least five rounds of mass drug administration (MDA) each with >65% coverage and with microfilaria (Mf) levels <1% in the monitored sites form the basis for stopping the MDA. Despite its rigour, this multi-step process is likely to miss sites with transmission potential (‘hotspots’) and its statistical assumptions for sampling and threshold levels for decision-making have not been validated. We addressed these issues in a large-scale epidemiological study in two primary health centres in Thanjavur district, India, endemic for bancroftian filariasis that had undergone eight rounds of MDA.Methodology/Principal Findings
The prevalence and intensity of Mf (per 60 µl blood) were 0.2% and 0.004 respectively in the survey that covered >70% of 50,363 population. The corresponding values for Ag were 2.3% and 17.3 Ag-units respectively. Ag-prevalence ranged from 0.7 to 0.9%, in children (2–10 years) and 2.7 to 3.0% in adults. Although the Mf-levels in the survey and the sentinel/spot check sites were <1% and Ag-level was <2% in children, we identified 7 “residual” (Mf-prevalence ≥1%, irrespective of Ag-status in children) and 17 “transmission” (at least one Ag-positive child born during the MDA period) hotspots. Antigenaemic persons were clustered both at household and site levels. We identified an Ag-prevalence of ∼1% in children (equivalent to 0.4% community Mf-prevalence) as a possible threshold value for stopping MDA.Conclusions/Significance
Existence of ‘hotspots’ and spatial clustering of infections in the study area indicate the need for developing good surveillance strategies for detecting ‘hotspots’, adopting evidence-based sampling strategies and evaluation unit size for TAS. 相似文献15.
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Liver-specific deletion of histone deacetylase 3 disrupts metabolic transcriptional networks 总被引:1,自引:0,他引:1
Knutson SK Chyla BJ Amann JM Bhaskara S Huppert SS Hiebert SW 《The EMBO journal》2008,27(7):1017-1028
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Brca2 (XRCC11) Deficiency Results in Radioresistant DNA Synthesis and a Higher Frequency of Spontaneous Deletions 总被引:1,自引:0,他引:1
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Maria Kraakman-van der Zwet Wilhelmina J. I. Overkamp Rebecca E. E. van Lange Jeroen Essers Annemarie van Duijn-Goedhart Ingrid Wiggers Srividya Swaminathan Paul P. W. van Buul Abdellatif Errami Raoul T. L. Tan Nicolaas G. J. Jaspers Shyam K. Sharan Roland Kanaar Magorzata Z. Zdzienicka 《Molecular and cellular biology》2002,22(2):669-679
We show here that the radiosensitive Chinese hamster cell mutant (V-C8) of group XRCC11 is defective in the breast cancer susceptibility gene Brca2. The very complex phenotype of V-C8 cells is complemented by a single human chromosome 13 providing the BRCA2 gene, as well as by the murine Brca2 gene. The Brca2 deficiency in V-C8 cells causes hypersensitivity to various DNA-damaging agents with an extreme sensitivity toward interstrand DNA cross-linking agents. Furthermore, V-C8 cells show radioresistant DNA synthesis after ionizing radiation, suggesting that Brca2 deficiency affects cell cycle checkpoint regulation. In addition, V-C8 cells display tremendous chromosomal instability and a high frequency of abnormal centrosomes. The mutation spectrum at the hprt locus showed that the majority of spontaneous mutations in V-C8 cells are deletions, in contrast to wild-type V79 cells. A mechanistic explanation for the genome instability phenotype of Brca2-deficient cells is provided by the observation that the nuclear localization of the central DNA repair protein in homologous recombination, Rad51, is reduced in V-C8 cells. 相似文献
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