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1.
Scaffolding proteins are involved in the incorporation, anchoring, maintenance, and removal of AMPA receptors (AMPARs) at synapses, either through a direct interaction with AMPARs or via indirect association through auxiliary subunits of transmembrane AMPAR regulatory proteins (TARPs). Synaptic scaffolding molecule (S-SCAM) is a newly characterized member of the scaffolding proteins critical for the regulation and maintenance of AMPAR levels at synapses, and directly binds to TARPs through a PDZ interaction. However, the functional significance of S-SCAM–TARP interaction in the regulation of AMPARs has not been tested. Here we show that overexpression of the C-terminal peptide of TARP-γ2 fused to EGFP abolished the S-SCAM-mediated enhancement of surface GluA2 expression. Conversely, the deletion of the PDZ-5 domain of S-SCAM that binds TARPs greatly attenuated the S-SCAM-induced increase of surface GluA2 expression. In contrast, the deletion of the guanylate kinase domain of S-SCAM did not show a significant effect on the regulation of AMPARs. Together, these results suggest that S-SCAM is regulating AMPARs through TARPs. 相似文献
2.
Melanie Krüger RoosAnne Samsom Loes A. Oosterhoff Monique E. van Wolferen Hans S. Kooistra Niels Geijsen Louis C. Penning Linda M. Kock Pilar SainzArnal Pedro M. Baptista Bart Spee 《Journal of cellular and molecular medicine》2022,26(19):4949
In Europe alone, each year 5500 people require a life‐saving liver transplantation, but 18% die before receiving one due to the shortage of donor organs. Whole organ engineering, utilizing decellularized liver scaffolds repopulated with autologous cells, is an attractive alternative to increase the pool of available organs for transplantation. The development of this technology is hampered by a lack of a suitable large‐animal model representative of the human physiology and a reliable and continuous cell source. We have generated porcine intrahepatic cholangiocyte organoids from adult stem cells and demonstrate that these cultures remained stable over multiple passages whilst retaining the ability to differentiate into hepatocyte‐ and cholangiocyte‐like cells. Recellularization onto porcine scaffolds was efficient and the organoids homogeneously differentiated, even showing polarization. Our porcine intrahepatic cholangiocyte system, combined with porcine liver scaffold paves the way for developing whole liver engineering in a relevant large‐animal model. 相似文献
3.
《Critical reviews in biochemistry and molecular biology》2013,48(3):201-235
AbstractClostridium thermocellum produces a highly active cellulase system that consists of a high-Mr multienzyme complex termed cellulosome. Hydrolytic components of the cellulosome are organized around a large, noncatalytic glycoprotein termed CipA that acts both as a scaffolding component and a cellulose-binding factor. Catalytic subunits of the cellulosome bear conserved, noncatalytic subdomains, termed dockerin domains, which bind to receptor domains of CipA, termed cohesin domains. CipA includes nine cohesin domains, a cellulose-binding domain, and a specialized dockerin domain. Proteins of the cell envelope carrying cohesin domains that specifically bind the dockerin domain of CipA have been identified. These proteins may mediate anchoring of the cellulosomes to the cell surface. Cellulase complexes similar to the cellulosome of C. thermocellum are produced by several cellulolytic clostridia. High-Mr multienzyme complexes have also been identified in anaerobic rumen fungi. The architecture of the fungal complexes also seems to rely on the interaction of conserved, noncatalytic docking domains with a scaffolding component. However, the sequence of the fungal docking domains bears no resemblance to the clostridial dockerin domains, suggesting that the fungal and clostridial complexes arose independently. 相似文献
4.
Improved white spruce (Picea glauca) genome assemblies and annotation of large gene families of conifer terpenoid and phenolic defense metabolism 下载免费PDF全文
René L. Warren Christopher I. Keeling Macaire Man Saint Yuen Anthony Raymond Greg A. Taylor Benjamin P. Vandervalk Hamid Mohamadi Daniel Paulino Readman Chiu Shaun D. Jackman Gordon Robertson Chen Yang Brian Boyle Margarete Hoffmann Detlef Weigel David R. Nelson Carol Ritland Nathalie Isabel Barry Jaquish Alvin Yanchuk Jean Bousquet Steven J. M. Jones John MacKay Inanc Birol Joerg Bohlmann 《The Plant journal : for cell and molecular biology》2015,83(2):189-212
5.
Yi-Fei Lu Xiao-Feng Jin Hiroshi Ikeda Okihito Yano Carmen Benítez-Benítez Wei-Jie Chen Yong-Di Liu Pedro Jiménez-Mejías Ming-Jian Yu 《植物分类学报:英文版》2021,59(4):668-686
Carex sect. Confertiflorae s.l. is a medium-sized species group (ca. 40 species) with its center of diversity in E Asia (China and Japan). According to morphological traits, the section has been proposed to split into two sections (sects. Confertiflorae sensu Ohwi and Molliculae Ohwi) up to five different ones (sects. Confertiflorae s.s., Molliculae, Dispalatae Ohwi, Ischnostachyae Ohwi, and Alliiformes Akiyama). Recent phylogenetic reconstructions showed Confertiflorae s.l. not to be monophyletic, as species traditionally considered part of it were found to belong to other clades, whereas species traditionally ascribed to other sections were nested within it. In this study, we investigated the phylogenetic structure, morphological affinities, and biogeographic history of sect. Confertiflorae s.l. We employed a taxon-based approach to explore the morphological affinities of the species considered in sect. Confertiflorae and compared the micromorphology of the nutlets of almost all the taxa using SEM. We included 40 samples representing 31 species/subspecies of sect. Confertiflorae s.l. and used two nuclear (ETS and ITS) and three plastid (trnL-F, matK, and rpl32-trnL UAG) molecular markers to reconstruct the phylogeny of the group. The phylogenetic analyses confirmed the polyphyly of sect. Confertiflorae s.l., whose representatives were found within five distinct clades. From these, two clades, sect. Confertiflorae and sect. Molliculae, were found to be closely related and contained the majority of the species. The composition of the two clades agreed with the morphological structure of the group, and we confirmed an exclusive combination of features (namely color of basal sheaths, presence of bract sheath, peduncle of lowest spike, inflorescence sex distribution, shape of pistillate glume apex, and color and veins of utricle, among others) characterizing each of the two clades. The origin of the two clades was found to be in the early Pliocene; however, the majority of the diversification events within each clade took place during the Pleistocene. This illustrates that although Asia has been regarded as having little potential ecological space for Carex to diversify due to its climate stability, groups of sedges sub-endemic from that area may have a fairly recent origin related to glaciations. We proposed the rearrangement of sect. Confertiflorae as previously conceived as three independent sections: the monotypic Alliiformes, sect. Molliculae, and sect. Paludosae. 相似文献
6.
Ruth Nussinov Hyunbum Jang Chung‐Jung Tsai 《Biological reviews of the Cambridge Philosophical Society》2015,90(2):587-598
Nanoclusters are anchored to membranes, either within them or in the cytoplasm latched onto the cytoskeleton, whose reorganization can regulate their activity. Nanoclusters have been viewed in terms of cooperativity and activation; here we perceive nanocluster organization from a conformational standpoint. This leads us to suggest that while single molecules encode activity, nanoclusters induce specificity, and that this is their main evolutionary aim. Distinct, isoform‐specific nanocluster organization can drive the preferred effector (and ligand) interactions and thereby designate signalling pathways. The absence of detailed structural information across the nanocluster, due to size and dynamics, hinders an in‐depth grasp of its mechanistic features; however, available data already capture some of the principles and their functional ‘raison d'être’. Collectively, clustering lends stability and reduces the likelihood of proteolytic cleavage; it also increases the effective local concentration and enables efficient cooperative activation. However, clustering does not determine the ability of the single molecule to function. Drugs targeting nanoclusters can attenuate activity by hampering cooperativity; however, this may not perturb activation and signalling, which originate from the molecules themselves, and as such, are likely to endure. What then is the major role of nanoclustering? Assuming that single molecules evolved first, with a subsequent increase in cellular complexity and emergence of highly similar isoform variants, evolution faced the threat of signalling promiscuity. We reason that this potential risk was thwarted by oligomerization and clustering; clustering confers higher specificity, and a concomitant extra layer of cellular control. In our Ras example, signalling will be more accurate as a dimer than as a monomer, where its isomer specificity could be compromised. 相似文献
7.
Gaillard S Bailly Y Benoist M Rakitina T Kessler JP Fronzaroli-Molinières L Dargent B Castets F 《Traffic (Copenhagen, Denmark)》2006,7(1):74-84
Striatin, SG2NA and zinedin, the three mammalian members of the striatin family are multimodular WD-repeat, calmodulin and calveolin-binding proteins. These scaffolding proteins, involved in both signaling and trafficking, are highly expressed in neurons. Using ultrastructural immunolabeling, we showed that, in Purkinje cells and hippocampal neurons, SG2NA is confined to the somatodendritic compartment with the highest density in dendritic spines. In cultured hippocampal neurons, SG2NA is also highly concentrated in dendritic spines. By expressing truncated forms of HA-tagged SG2NAbeta, we demonstrated that the coiled-coil domain plays an essential role in the targeting of SG2NA within spines. Furthermore, co-immunoprecipitation experiments indicate that this coiled-coil domain is also crucial for the homo- and hetero-oligomerization of these proteins. Thus, oligomerization of the striatin family proteins is probably an obligatory step for their routing to the dendritic spines, and hetero-oligomerization explains why all these proteins are often co-expressed in the neurons of the rat brain and spinal cord. 相似文献
8.
Circular dichroism (CD) and NMR spectroscopy were used to study the conformational properties of two synthetic peptides, D82-R101 and D82-I109, encompassing the caveolin scaffolding domain (D82-R101), in the presence of dodecylphosphocholine (DPC) micelles. Our data show that a stable helical conformation of the caveolin scaffolding domain in a membrane mimicking system is only obtained for the peptide including the L102-I109 hydrophobic stretch, a part of the caveolin intra-membrane domain. Through chemical shift variations, an ensemble of six residues of the D82-L109 peptide, mainly located in the V(94)TKYWFYR(101) motif were found to detect the presence of phosphatidylserine solubilized in DPC micelles. Our results constitute a first step for elucidating at a residue level the conformational properties of the central region of the caveolin-1 protein. 相似文献
9.
Sorting nexin 27 interacts with the Cytohesin associated scaffolding protein (CASP) in lymphocytes 总被引:2,自引:0,他引:2
MacNeil AJ Mansour M Pohajdak B 《Biochemical and biophysical research communications》2007,359(4):848-853
CASP is a small cytokine-inducible protein, primarily expressed in hematopoetic cells, which associates with members of the Cytohesin/ARNO family of guanine nucleotide-exchange factors. Cytohesins activate ARFs, a group of GTPases involved in vesicular initiation. Functionally, CASP is an adaptor protein containing a PDZ domain, a coiled-coil, and a potential carboxy terminal PDZ-binding motif that we sought to characterize here. Using GST pulldowns and mass spectrometry we identified the novel interaction of CASP and sorting nexin 27 (SNX27). In lymphocytes, CASP's PDZ-binding motif interacts with the PDZ domain of SNX27. This protein is a unique member of the sorting nexin family of proteins, a group generally involved in the endocytic and intracellular sorting machinery. Endogenous SNX27 and CASP co-localize at the early endosomal compartment in lymphocytes and also in transfection studies. These results suggest that endosomal SNX27 may recruit CASP to orchestrate intracellular trafficking and/or signaling complexes. 相似文献
10.
Brevican distinctively assembles extracellular components at the large diameter nodes of Ranvier in the CNS 总被引:1,自引:0,他引:1
Yoko Bekku Uwe Rauch† Yoshifumi Ninomiya Toshitaka Oohashi 《Journal of neurochemistry》2009,108(5):1266-1276
Brevican is known to be an abundant extracellular matrix component in the adult brain and a structural constituent of perineuronal nets. We herein show that brevican, tenascin-R (TN-R) and phosphacan are present at the nodes of Ranvier on myelinated axons with a particularly large diameter in the central nervous system. A brevican deficiency resulted in a reorganization of the nodal matrices, which was characterized by the shift of TN-R, and concomitantly phosphacan, from an axonal diameter-dependent association with nodes to an axonal diameter independent association. Supported by the co-immunoprecipitation results, these observations indicate that the presence of TN-R and phosphacan at nodes is normally brevican-dependent, while in the absence of brevican these molecules can also be recruited by versican V2. The versican V2 and Bral1 distribution was not affected, thus indicating a brevican-independent role of these two molecules for establishing hyaluronan-binding matrices at the nodes. Our results revealed that brevican plays a crucial role in determining the specialization of the hyaluronan-binding nodal matrix assemblies in large diameter nodes. 相似文献