المؤلفون: Trovò, Luca, Kouvaros, Stylianos, Schwenk, Jochen, Fernandez-Fernandez, Diego, Fritzius, Thorsten, Rem, Pascal Dominic, Früh, Simon, Gassmann, Martin, Fakler, Bernd, Bischofberger, Josef, Bettler, Bernhard

المصدر: EMBO Rep ; ISSN:1469-3178 ; Volume:25 ; Issue:6

مصطلحات موضوعية: Cav2.2, GABA-B, KCTD16, Receptor Signaling Complex Assembly, Transport Vesicle

الوصف: GABAB receptors (GBRs), the G protein-coupled receptors for GABA, regulate synaptic transmission throughout the brain. A main synaptic function of GBRs is the gating of Cav2.2-type Ca2+ channels. However, the cellular compartment where stable GBR/Cav2.2 signaling complexes form remains unknown. In this study, we demonstrate that the vesicular protein synaptotagmin-11 (Syt11) binds to both the auxiliary GBR subunit KCTD16 and Cav2.2 channels. Through these dual interactions, Syt11 recruits GBRs and Cav2.2 channels to post-Golgi vesicles, thus facilitating assembly of GBR/Cav2.2 signaling complexes. In addition, Syt11 stabilizes GBRs and Cav2.2 channels at the neuronal plasma membrane by inhibiting constitutive internalization. Neurons of Syt11 knockout mice exhibit deficits in presynaptic GBRs and Cav2.2 channels, reduced neurotransmitter release, and decreased GBR-mediated presynaptic inhibition, highlighting the critical role of Syt11 in the assembly and stable expression of GBR/Cav2.2 complexes. These findings support that Syt11 acts as a vesicular scaffold protein, aiding in the assembly of signaling complexes from low-abundance components within transport vesicles. This mechanism enables insertion of pre-assembled functional signaling units into the synaptic membrane.

العلاقة: https://doi.org/10.1038/s44319-024-00147-0Test; https://pubmed.ncbi.nlm.nih.gov/38698221Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169412Test/

الإتاحة: https://doi.org/10.1038/s44319-024-00147-0Test
https://pubmed.ncbi.nlm.nih.gov/38698221Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11169412Test/

المؤلفون: Matsuoka, Ken, Schekman, Randy, Orci, Lelio, Heuser, John E.

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2001 Nov . 98(24), 13705-13709.

الوصول الحر: https://www.jstor.org/stable/3057158Test

المؤلفون: Shimoni, Yuval, Kurihara, Tatsuo, Ravazzola, Mariella, Amherdt, Mylène, Orci, Lelio, Schekman, Randy

المصدر: The Journal of Cell Biology, 2000 Nov . 151(5), 973-984.

الوصول الحر: https://www.jstor.org/stable/1620239Test

المؤلفون: Roberg, Kevin J., Crotwell, Michelle, Espenshade, Peter, Gimeno, Ruth, Kaiser, Chris A.

المصدر: The Journal of Cell Biology, 1999 May . 145(4), 659-672.

الوصول الحر: https://www.jstor.org/stable/1619216Test

المؤلفون: Kwon, EK, Kang, TW, Oh, T, Choo, OS, Ye, YM, Park, HS, Ban, GY

المساهمون: 103726, 101472, Ye, YM, Park, HS

مصطلحات موضوعية: Aspirin, asthma, hypersensitivity, multiomics, transport vesicle

الوصف: Dysregulation of the arachidonic acid metabolic pathway is the most widely known pathomechanism of aspirin-exacerbated respiratory disease (AERD). This study aimed to perform integrative analysis of transcriptomic and epigenomic profiling with network analysis to determine the novel pathogenic features of AERD. Ten patients with asthma including 5 patients with AERD and another 5 patients with aspirin tolerant asthma (ATA) were enrolled. Nasal scraping was performed and nasal mucosa was used in omics profiling. Peripheral eosinophil counts, sputum eosinophil counts, fractional exhaled nitric oxide levels, and pulmonary function test results were evaluated. Differentially expressed genes (DEGs), differentially methylated probes (DMPs) and differentially correlated genes (DCGs) between patients with AERD and those with ATA were analyzed. Network analysis using ingenuity pathway analysis (IPA) was performed to determine the gene connection network and signaling pathways. In total, 1,736 DEGs, 1,401 DMPs, and 19 pairs for DCGs were identified. Among DCGs, genes related to vesicle transport (e.g., RAB3B and STX2) and sphingolipid dysregulation (e.g., SMPD3) were found to be hypo-methylated and up-regulated in AERD. Using the canonical pathway analysis of IPA with 78 asthma-related DEGs, signaling pathways of T helper cell differentiation/activation and Fcε receptor I were generated. Up-regulation of RORγt and FcER1A were noted in AERD. Gene expression levels of RAB3B, SYNE1, STX2, SMPD3 and RORγt were significantly associated with sputum eosinophil counts. Quantitative real-time polymerase chain reaction was performed and mRNA expression levels of STX2, SMPD3, RORγt, and FcER1A were significantly higher in AERD compared to ATA. Distinct pathogenic features were identified by using integrative multi-omics data analysis in patients with AERD.

العلاقة: J020927355; http://repository.ajou.ac.kr/handle/201003/32046Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570783Test; Allergy, asthma & immunology research, 15(5). : 682-694, 2023

الإتاحة: https://doi.org/10.4168/aair.2023.15.5.682Test
http://repository.ajou.ac.kr/handle/201003/32046Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10570783Test

المؤلفون: Maud Magdeleine, Romain Gautier, Pierre Gounon, Hélène Barelli, Stefano Vanni, Bruno Antonny

المصدر: eLife, Vol 5 (2016)

مصطلحات موضوعية: ALPS motif, membrane curvature, golgin, Golgi, transport vesicle, perforated cell, Medicine, Science, Biology (General), QH301-705.5

الوصف: When small phosphatidylcholine liposomes are added to perforated cells, they bind preferentially to the Golgi suggesting an exceptional avidity of this organelle for curved membranes without stereospecific interactions. We show that the cis golgin GMAP-210 accounts for this property. First, the liposome tethering properties of the Golgi resembles that of the amphipathic lipid-packing sensor (ALPS) motif of GMAP-210: both preferred small (radius < 40 nm) liposomes made of monounsaturated but not saturated lipids. Second, reducing GMAP-210 levels or redirecting its ALPS motif to mitochondria decreased liposome capture by the Golgi. Extensive mutagenesis analysis suggests that GMAP-210 tethers authentic transport vesicles via the same mechanism whereby the ALPS motif senses lipid-packing defects at the vesicle surface through its regularly spaced hydrophobic residues. We conclude that the Golgi uses GMAP-210 as a filter to select transport vesicles according to their size and bulk lipid composition.

وصف الملف: electronic resource

العلاقة: https://elifesciences.org/articles/16988Test; https://doaj.org/toc/2050-084XTest

الوصول الحر: https://doaj.org/article/25d0ecff4dd64d5b948bd1e97aadd927Test

المؤلفون: Pak-yan Patricia Cheung, Suzanne R. Pfeffer

المصدر: Frontiers in Cell and Developmental Biology, Vol 4 (2016)

مصطلحات موضوعية: Golgi, Atomic Force Microscopy, membrane traffic, Transport vesicle, Coiled coil protein, Biology (General), QH301-705.5

الوصف: The Golgi complex is decorated with so-called Golgin proteins that share a common feature: a large proportion of their amino acid sequences are predicted to form coiled-coil structures. The possible presence of extensive coiled coils implies that these proteins are highly elongated molecules that can extend a significant distance from the Golgi surface. This property would help them to capture or trap inbound transport vesicles and to tether Golgi mini-stacks together. This review will summarize our current understanding of coiled coil tethers that are needed for the receipt of transport vesicles at the trans Golgi network. How do long tethering proteins actually catch vesicles? Golgi-associated, coiled coil tethers contain numerous binding sites for small GTPases, SNARE proteins, and vesicle coat proteins. How are these interactions coordinated and are any or all of them important for the tethering process? Progress towards understanding these questions and remaining, unresolved mysteries will be discussed.

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/Journal/10.3389/fcell.2016.00018/fullTest; https://doaj.org/toc/2296-634XTest

الوصول الحر: https://doaj.org/article/3501622d677f4c3db3f2bb8993ff125fTest

المؤلفون: Foret, Lionel, Sens, Pierre

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2008 Sep . 105(39), 14763-14768.

الوصول الحر: https://www.jstor.org/stable/25464309Test

المؤلفون: Heuvingh, Julien, Franco, Michel, Chavrier, Philippe, Sykes, Cécile

المصدر: Proceedings of the National Academy of Sciences of the United States of America, 2007 Oct . 104(43), 16928-16933.

الوصول الحر: https://www.jstor.org/stable/25450159Test

المؤلفون: Wang Zhang, Yifei Gu, Hongda Wang, Shengkun Yu, Haiyang Wang, Zhiguo Lin, Meng Na, Zhibin Han, Long Mu, Hongmei Wu, Tianyu Wang

مصطلحات موضوعية: Hippocampal sclerosis, Messenger RNA, Nucleosome assembly, General transcription factor, Transport vesicle membrane, Cell Biology, General Medicine, Biology, Hippocampal formation, medicine.disease, Cell biology, Cellular and Molecular Neuroscience, FYN, Circular RNA, medicine

الوصف: Hippocampal sclerosis (HS) is the most common surgical pathology associated with temporal lobe epilepsy (TLE). However, the cause of TLE with or without HS remains unknown. Our current study aimed to illustrate the essential molecular mechanism that is potentially involved in the pathogenesis of TLE-HS and to shed light on the transcriptional changes associated with hippocampal sclerosis. Compared to no-HS group, 341 mRNA transcripts and 131 circRNA transcripts were differentially expressed in ILAE type 1 group. The raw sequencing data have been deposited into sequence read archive (SRA) database under accession number PRJNA699348.Gene Ontology analysis demonstrated that the dysregulated genes were associated with the biological processes of vesicle-mediated transport. Enrichment analysis demonstrated that dysregulated genes were involved mainly in the MAPK signal pathway. Subsequently, A total of 441 known or predicted interactions were formed among DEGs, and the most important module was detected in the PPI network using the MCODE plug-in. There were mainly four functional modules enriched: ER to Golgi transport vesicle membrane, Basal transcription factors, GABA-gated chloride ion channel activity, CENP-A containing nucleosome assembly. A circRNA-mRNA co-expression network was constructed including 5 circRNAs(hsa_circ_0025349, hsa_circ_0002405, hsa_circ_0004805, hsa_circ_0032254, and hsa_circ_0032875) and three mRNAs (FYN, SELENBP1, and GRIPAP1) based on the normalized mRNA signal intensities. This is the first to report the circRNAs and mRNAs expression profile of surgically resected hippocampal tissues from TLE patients of ILAE-1 and no-HS, and these results may provide new insight into the transcriptional changes associated with this pathology.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::50a25a3098dee865bf8acf2a9b466bf9Test
https://doi.org/10.21203/rs.3.rs-331427/v2Test