The Experts below are selected from a list of 87024 Experts worldwide ranked by ideXlab platform
Robert C Malenka - One of the best experts on this subject based on the ideXlab platform.
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leucine rich repeat Transmembrane Proteins are essential for maintenance of long term potentiation
Neuron, 2013Co-Authors: Gilberto J Solerllavina, Pamela Arstikaitis, Wade Morishita, Mohiuddin Ahmad, Thomas C Sudhof, Robert C MalenkaAbstract:Leucine-rich repeat Transmembrane Proteins (LRRTMs) are synaptic cell adhesion molecules that trigger excitatory synapse assembly in cultured neurons and influence synaptic function in vivo, but their role in synaptic plasticity is unknown. shRNA-mediated knockdown (KD) of LRRTM1 and LRRTM2 in vivo in CA1 pyramidal neurons of newborn mice blocked long-term potentiation (LTP) in acute hippocampal slices. Molecular replacement experiments revealed that the LRRTM2 extracellular domain is sufficient for LTP, probably because it mediates binding to neurexins (Nrxs). Examination of surface expression of endogenous AMPA receptors (AMPARs) in cultured neurons suggests that LRRTMs maintain newly delivered AMPARs at synapses after LTP induction. LRRTMs are also required for LTP of mature synapses on adult CA1 pyramidal neurons, indicating that the block of LTP in neonatal synapses by LRRTM1 and LRRTM2 KD is not due to impairment of synapse maturation.
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the neurexin ligands neuroligins and leucine rich repeat Transmembrane Proteins perform convergent and divergent synaptic functions in vivo
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Gilberto J Solerllavina, Thomas C Sudhof, Marc V Fuccillo, Robert C MalenkaAbstract:Synaptic cell adhesion molecules, including the neurexin ligands, neuroligins (NLs) and leucine-rich repeat Transmembrane Proteins (LRRTMs), are thought to organize synapse assembly and specify synapse function. To test the synaptic role of these molecules in vivo, we performed lentivirally mediated knockdown of NL3, LRRTM1, and LRRTM2 in CA1 pyramidal cells of WT and NL1 KO mice at postnatal day (P)0 (when synapses are forming) and P21 (when synapses are largely mature). P0 knockdown of NL3 in WT or NL1 KO neurons did not affect excitatory synaptic transmission, whereas P0 knockdown of LRRTM1 and LRRTM2 selectively reduced AMPA receptor-mediated synaptic currents. P0 triple knockdown of NL3 and both LRRTMs in NL1 KO mice yielded greater reductions in AMPA and NMDA receptor-mediated currents, suggesting functional redundancy between NLs and LRRTMs during early synapse development. In contrast, P21 knockdown of LRRTMs did not alter excitatory transmission, whereas NL manipulations supported a role for NL1 in maintaining NMDA receptor-mediated transmission. These results show that neurexin ligands in vivo form a dynamic synaptic cell adhesion network, with compensation between NLs and LRRTMs during early synapse development and functional divergence upon synapse maturation.
James M. Anderson - One of the best experts on this subject based on the ideXlab platform.
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phosphorylation of tight junction Transmembrane Proteins many sites much to do
Tissue barriers, 2018Co-Authors: Christina M Van Itallie, James M. AndersonAbstract:Phosphorylation is a dynamic post-translational modification that can alter protein structure, localization, protein-protein interactions and stability. All of the identified tight junction Transmembrane Proteins can be multiply phosphorylated, but only in a few cases are the consequences of phosphorylation at specific sites well characterized. The goal of this review is to highlight some of the best understood examples of phosphorylation changes in the integral membrane tight junction Proteins in the context of more general overview of the effects of phosphorylation throughout the proteome. We expect as that structural information for the tight junction Proteins becomes more widely available and the molecular modeling algorithms improve, so will our understanding of the relevance of phosphorylation changes at single and multiple sites in tight junction Proteins.
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Transmembrane Proteins in the Tight Junction Barrier
Journal of the American Society of Nephrology : JASN, 1999Co-Authors: Alan S. Fanning, Laura L. Mitic, James M. AndersonAbstract:Three types of Transmembrane Proteins have been identified within the tight junction, but it remains to be determined how they provide the molecular basis for regulating the paracellular permeability for water, solutes, and immune cells. Several of these Proteins localize specifically within the continuous cell-to-cell contacts of the tight junction. One of these, occludin, is a cell adhesion molecule that has been demonstrated to influence ion and solute permeability. The claudins are a family of four-membrane spanning Proteins; unexpectedly, other members of this family have already been characterized without recognizing their relationship to tight junctions. Junction adhesion molecule, the most recently identified tight junction component, is a member of the Ig superfamily and influences the paracellular transmigration of immune cells. A plaque of cytoplasmic Proteins under the junction may be responsible for scaffolding the Transmembrane Proteins, creating a link to the perijunctional actin cytoskeleton and transducing regulatory signals that control the paracellular barrier.
Arne Elofsson - One of the best experts on this subject based on the ideXlab platform.
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topology of membrane Proteins predictions limitations and variations
Current Opinion in Structural Biology, 2018Co-Authors: Konstantinos D Tsirigos, Arne Elofsson, Sudha Govindarajan, Claudio Bassot, Ake Vastermark, John Lamb, Nanjiang ShuAbstract:Transmembrane Proteins perform a variety of important biological functions necessary for the survival and growth of the cells. Membrane Proteins are built up by Transmembrane segments that span the lipid bilayer. The segments can either be in the form of hydrophobic alpha-helices or beta-sheets which create a barrel. A fundamental aspect of the structure of Transmembrane Proteins is the membrane topology, that is, the number of Transmembrane segments, their position in the protein sequence and their orientation in the membrane. Along these lines, many predictive algorithms for the prediction of the topology of alpha-helical and beta-barrel Transmembrane Proteins exist. The newest algorithms obtain an accuracy close to 80% both for alpha-helical and beta-barrel Transmembrane Proteins. However, lately it has been shown that the simplified picture presented when describing a protein family by its topology is limited. To demonstrate this, we highlight examples where the topology is either not conserved in a protein superfamily or where the structure cannot be described solely by the topology of a protein. The prediction of these non-standard features from sequence alone was not successful until the recent revolutionary progress in 3D-structure prediction of Proteins.
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structural classification and prediction of reentrant regions in α helical Transmembrane Proteins application to complete genomes
Journal of Molecular Biology, 2006Co-Authors: Hakan Viklund, Erik Granseth, Arne ElofssonAbstract:Abstract Alongside the well-studied membrane spanning helices, α-helical Transmembrane (TM) Proteins contain several functionally and structurally important types of substructures. Here, existing 3D structures of Transmembrane Proteins have been used to define and study the concept of reentrant regions, i.e. membrane penetrating regions that enter and exit the membrane on the same side. We find that these regions can be divided into three distinct categories based on secondary structure motifs, namely long regions with a helix–coil–helix motif, regions of medium length with the structure helix–coil or coil–helix and regions of short to medium length consisting entirely of irregular secondary structure. The residues situated in reentrant regions are significantly smaller on average compared to other regions and reentrant regions can be detected in the inter-Transmembrane loops with an accuracy of ∼ 70% based on their amino acid composition. Using TOP-MOD, a novel method for predicting reentrant regions, we have scanned the genomes of Escherichia coli, Saccharomyces cerevisiae and Homo sapiens. The results suggest that more than 10% of Transmembrane Proteins contain reentrant regions and that the occurrence of reentrant regions increases linearly with the number of Transmembrane regions. Reentrant regions seem to be most commonly found in channel Proteins and least commonly in signal receptors.
Jurgen Schneiderschaulies - One of the best experts on this subject based on the ideXlab platform.
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tetraspanins small Transmembrane Proteins with big impact on membrane microdomain structures
Communicative & Integrative Biology, 2008Co-Authors: Katrin Singethan, Jurgen SchneiderschauliesAbstract:: Members of the tetraspanin family of Transmembrane Proteins including CD9, CD37, CD53, CD63, CD81, CD82, CD151, etc., contribute to the structural organization of the plasma membrane by forming microdomain structures, influencing cell fusion and regulating cell motility. Interestingly, K41, a CD9-specific monoclonal antibody (mAb), inhibits the release of human immunodeficiency virus (HIV-1), and the canine distemper virus (CDV)-, but not measles virus (MV)-induced cell-cell fusion. This mAb, which recognizes a conformational epitope on the large extracellular loop (LEL) of CD9, induced rapid relocation and clustering of CD9 in net-like structures at cell-cell contact areas.1 High-resolution analyses revealed that CD9 clustering is accompanied by the formation of microvilli that protrude from either side of adjacent cell surfaces, thus forming structures like microvilli zippers. While the cellular CD9-associated Proteins beta1-integrin and EWI-F were co-clustered with CD9 at cell-cell interfaces, viral Proteins in infected cells were differentially affected. MV envelope Proteins were detected within, whereas CDV Proteins were excluded from CD9 clusters, and thus, the tetraspanin CD9 can regulate cell-cell fusion by controlling the access of the viral fusion machinery to cell contact areas.
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tetraspanins small Transmembrane Proteins with big impact on membrane microdomain structures
Communicative & Integrative Biology, 2008Co-Authors: Katrin Singethan, Jurgen SchneiderschauliesAbstract:: Members of the tetraspanin family of Transmembrane Proteins including CD9, CD37, CD53, CD63, CD81, CD82, CD151, etc., contribute to the structural organization of the plasma membrane by forming microdomain structures, influencing cell fusion and regulating cell motility. Interestingly, K41, a CD9-specific monoclonal antibody (mAb), inhibits the release of human immunodeficiency virus (HIV-1), and the canine distemper virus (CDV)-, but not measles virus (MV)-induced cell-cell fusion. This mAb, which recognizes a conformational epitope on the large extracellular loop (LEL) of CD9, induced rapid relocation and clustering of CD9 in net-like structures at cell-cell contact areas.1 High-resolution analyses revealed that CD9 clustering is accompanied by the formation of microvilli that protrude from either side of adjacent cell surfaces, thus forming structures like microvilli zippers. While the cellular CD9-associated Proteins beta1-integrin and EWI-F were co-clustered with CD9 at cell-cell interfaces, viral Proteins in infected cells were differentially affected. MV envelope Proteins were detected within, whereas CDV Proteins were excluded from CD9 clusters, and thus, the tetraspanin CD9 can regulate cell-cell fusion by controlling the access of the viral fusion machinery to cell contact areas.
Gilberto J Solerllavina - One of the best experts on this subject based on the ideXlab platform.
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leucine rich repeat Transmembrane Proteins are essential for maintenance of long term potentiation
Neuron, 2013Co-Authors: Gilberto J Solerllavina, Pamela Arstikaitis, Wade Morishita, Mohiuddin Ahmad, Thomas C Sudhof, Robert C MalenkaAbstract:Leucine-rich repeat Transmembrane Proteins (LRRTMs) are synaptic cell adhesion molecules that trigger excitatory synapse assembly in cultured neurons and influence synaptic function in vivo, but their role in synaptic plasticity is unknown. shRNA-mediated knockdown (KD) of LRRTM1 and LRRTM2 in vivo in CA1 pyramidal neurons of newborn mice blocked long-term potentiation (LTP) in acute hippocampal slices. Molecular replacement experiments revealed that the LRRTM2 extracellular domain is sufficient for LTP, probably because it mediates binding to neurexins (Nrxs). Examination of surface expression of endogenous AMPA receptors (AMPARs) in cultured neurons suggests that LRRTMs maintain newly delivered AMPARs at synapses after LTP induction. LRRTMs are also required for LTP of mature synapses on adult CA1 pyramidal neurons, indicating that the block of LTP in neonatal synapses by LRRTM1 and LRRTM2 KD is not due to impairment of synapse maturation.
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the neurexin ligands neuroligins and leucine rich repeat Transmembrane Proteins perform convergent and divergent synaptic functions in vivo
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Gilberto J Solerllavina, Thomas C Sudhof, Marc V Fuccillo, Robert C MalenkaAbstract:Synaptic cell adhesion molecules, including the neurexin ligands, neuroligins (NLs) and leucine-rich repeat Transmembrane Proteins (LRRTMs), are thought to organize synapse assembly and specify synapse function. To test the synaptic role of these molecules in vivo, we performed lentivirally mediated knockdown of NL3, LRRTM1, and LRRTM2 in CA1 pyramidal cells of WT and NL1 KO mice at postnatal day (P)0 (when synapses are forming) and P21 (when synapses are largely mature). P0 knockdown of NL3 in WT or NL1 KO neurons did not affect excitatory synaptic transmission, whereas P0 knockdown of LRRTM1 and LRRTM2 selectively reduced AMPA receptor-mediated synaptic currents. P0 triple knockdown of NL3 and both LRRTMs in NL1 KO mice yielded greater reductions in AMPA and NMDA receptor-mediated currents, suggesting functional redundancy between NLs and LRRTMs during early synapse development. In contrast, P21 knockdown of LRRTMs did not alter excitatory transmission, whereas NL manipulations supported a role for NL1 in maintaining NMDA receptor-mediated transmission. These results show that neurexin ligands in vivo form a dynamic synaptic cell adhesion network, with compensation between NLs and LRRTMs during early synapse development and functional divergence upon synapse maturation.
