Liprin-α proteins: scaffold molecules for synapse maturation

2007 ◽  
Vol 35 (5) ◽  
pp. 1278-1282 ◽  
Author(s):  
S.A. Spangler ◽  
C.C. Hoogenraad
Keyword(s):  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Synaptic Proteins ◽  
Model Systems ◽  
Scaffolding Proteins ◽  
Synapse Maturation ◽  
Biochemical Genetic ◽  
Processing And Storage ◽  
And Function ◽  
And Storage

Synapses are specialized communication junctions between neurons whose plasticity provides the structural and functional basis for information processing and storage in the brain. Recent biochemical, genetic and imaging studies in diverse model systems are beginning to reveal the molecular mechanisms by which synaptic vesicles, ion channels, receptors and other synaptic components assemble to make a functional synapse. Recent evidence has shown that the formation and function of synapses are critically regulated by the liprin-α family of scaffolding proteins. The liprin-αs have been implicated in pre- and post-synaptic development by recruiting synaptic proteins and regulating synaptic cargo transport. Here, we will summarize the diversity of liprin binding partners, highlight the factors that control the function of liprin-αs at the synapse and discuss how liprin-α family proteins regulate synapse formation and synaptic transmission.

scholarly journals Liprin-α-Mediated Assemblies and Their Roles in Synapse Formation

2021 ◽  
Vol 9 ◽  
Author(s):  
Xingqiao Xie ◽  
Mingfu Liang ◽  
Cong Yu ◽  
Zhiyi Wei
Keyword(s):  
Synapse Formation ◽  
Protein Complexes ◽  
Synaptic Proteins ◽  
Model Systems ◽  
Genetic Studies ◽  
Binding Partners ◽  
Assembly Mechanism ◽  
Cellular Junctions ◽  
Organized Assemblies ◽  
And Function

Brain’s functions, such as memory and learning, rely on synapses that are highly specialized cellular junctions connecting neurons. Functional synapses orchestrate the assembly of ion channels, receptors, enzymes, and scaffold proteins in both pre- and post-synapse. Liprin-α proteins are master scaffolds in synapses and coordinate various synaptic proteins to assemble large protein complexes. The functions of liprin-αs in synapse formation have been largely uncovered by genetic studies in diverse model systems. Recently, emerging structural and biochemical studies on liprin-α proteins and their binding partners begin to unveil the molecular basis of the synaptic assembly. This review summarizes the recent structural findings on liprin-αs, proposes the assembly mechanism of liprin-α-mediated complexes, and discusses the liprin-α-organized assemblies in the regulation of synapse formation and function.

Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical circuit assembly

2020 ◽  
Author(s):  
Yajun Xie ◽  
Aaron T. Kuan ◽  
Wengang Wang ◽  
Zachary T. Herbert ◽  
Olivia Mosto ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Critical Role ◽  
Shh Signaling ◽  
Shh Pathway ◽  
Cortical Astrocytes ◽  
Functional Features ◽  
And Function ◽  
Circuit Assembly

SUMMARYNeuron-glia relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. Here we demonstrate that the canonical Sonic hedgehog (Shh) pathway is active in cortical astrocytes, where it acts to coordinate layer-specific synaptic connectivity and functional circuit development. We show that Ptch1 is a Shh receptor that is expressed by cortical astrocytes during development and that Shh signaling is necessary and sufficient to promote the expression of layer-specific astrocyte genes involved in regulating synapse formation and function. Loss of Shh in layer V neurons reduces astrocyte complexity and coverage by astrocytic processes in tripartite synapses, moreover, cell-autonomous activation of Shh signaling in astrocytes promotes cortical excitatory synapse formation. Together, these results suggest that Shh secreted from deep layer cortical neurons acts to specialize the molecular and functional features of astrocytes during development to shape circuit assembly and function.

scholarly journals Stability of tryptophan during food processing and storage

1985 ◽  
Vol 53 (2) ◽  
pp. 281-292 ◽  
Author(s):  
Henrik K. Nielsen ◽  
D. De Weck ◽  
P. A. Finot ◽  
R. Liardon ◽  
R. F. Hurrell
Keyword(s):  
Food Processing ◽  
Whey Proteins ◽  
Milk Powder ◽  
Protein Digestibility ◽  
Model Systems ◽  
Maillard Reactions ◽  
Minor Losses ◽  
Oxidation Of Methionine ◽  
Processing And Storage ◽  
And Storage

1. The stability of tryptophan was evaluated in several different food model systems using a chemical method (high pressure liquid chromatography after alkaline-hydrolysis) and rat assays. Losses of tryptophan were compared with the losses of lysine and methionine.2. Whey proteins stored in the presence of oxidizing lipids showed large losses of lysine and extensive methionine oxidation but only minor losses of tryptophan as measured chemically. The observed decrease in bioavailable tryptophan was explained by a lower protein digestibility.3. Casein treated with hydrogen peroxide to oxidize all methionine to methionine sulphoxide showed a 9% loss in bioavailable tryptophan.4. When casein was reacted with caffeic acid at pH 7 in the presence of monophenol monooxygenase (tyrosinase; EC 1.14.18.l), no chemical loss of tryptophan occurred, although fluorodinitrobenzene-reactive lysine fell by 23%. Tryptophan bioavailability fell IS%, partly due to an 8% reduction in protein digestibility.5. Alkali-treated casein (0.15 M-sodium hydroxide, 80°,4 h) did not support rat growth. Chemically-determined tryptophan, available tryptophan and true nitrogen digestibility fell 10, 46 and 23% respectively. Racemization of tryptophan was found to be 10% (D/(D+L)).6. In whole-milk powder, which had undergone ‘early’ or ‘advanced’ Maillard reactions, tryptophan, determined chemically or in rat assays, was virtually unchanged. Extensive lysine losses occurred.7. It was concluded that losses of tryptophan during food processing and storage are small and of only minor nutritional importance, especially when compared with much larger losses of lysine and the more extensive oxidation of methionine.

scholarly journals Wnt-Frizzled Signaling Regulates Activity-Mediated Synapse Formation

2021 ◽  
Vol 14 ◽  
Author(s):  
Samuel Teo ◽  
Patricia C. Salinas
Keyword(s):  
Wnt Signaling ◽  
Neuronal Activity ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Model Systems ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Wnt Ligands

The formation of synapses is a tightly regulated process that requires the coordinated assembly of the presynaptic and postsynaptic sides. Defects in synaptogenesis during development or in the adult can lead to neurodevelopmental disorders, neurological disorders, and neurodegenerative diseases. In order to develop therapeutic approaches for these neurological conditions, we must first understand the molecular mechanisms that regulate synapse formation. The Wnt family of secreted glycoproteins are key regulators of synapse formation in different model systems from invertebrates to mammals. In this review, we will discuss the role of Wnt signaling in the formation of excitatory synapses in the mammalian brain by focusing on Wnt7a and Wnt5a, two Wnt ligands that play an in vivo role in this process. We will also discuss how changes in neuronal activity modulate the expression and/or release of Wnts, resulting in changes in the localization of surface levels of Frizzled, key Wnt receptors, at the synapse. Thus, changes in neuronal activity influence the magnitude of Wnt signaling, which in turn contributes to activity-mediated synapse formation.

scholarly journals A Review: Microbial Diversity and Function of Fermented Meat Products in China

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengli Wang ◽  
Zhengxi Wang ◽  
Lili Ji ◽  
Jiamin Zhang ◽  
Zhiping Zhao ◽  
...  
Keyword(s):  
Microbial Diversity ◽  
Raw Materials ◽  
Meat Products ◽  
Safety Control ◽  
Processing And Storage ◽  
Yeasts And Molds ◽  
And Function ◽  
And Storage ◽  
Fermentation Technology ◽  
Growth And Reproduction

Fermented meat products have a long history in China. These products exhibit a characteristic unique flavor, compact meat quality, clear color, long shelf life and wide variety and are easy to transport. During the processing and storage of fermented meat products, microorganisms are present and exhibit diverse characteristics. Microorganisms can accelerate the degradation of proteins and fats to produce flavor compounds, inhibit the growth and reproduction of heterozygous bacteria, and reduce the content of chemical pollutants. This paper reviews the microbial diversity of Chinese ham, sausage, preserved meat, pressed salted duck, preserved fish and air-dried meat and provides analyses of the microbial compositions of various products. Due to the differences in raw materials, technology, auxiliary materials, and fermentation technology, the microbial species found in various fermented meat products in China are different. However, most fermented meat products in China are subjected to pickling and fermentation, so their microbial compositions also have similarities. Microorganisms in fermented meat products mainly include staphylococci, lactobacilli, micrococci, yeasts, and molds. The study of microbial diversity is of great significance for the formation of quality flavor and the safety control of fermented meat products, and it provides some theoretical reference for the study of fermented meat products in China.

scholarly journals Stability of tryptophan during food processing and storage

1985 ◽  
Vol 53 (2) ◽  
pp. 293-300 ◽  
Author(s):  
Henrik K. Nielsen ◽  
A. Klein ◽  
R. F. Hurrell
Keyword(s):  
Alkaline Hydrolysis ◽  
Food Processing ◽  
Model Systems ◽  
Chemical Methods ◽  
Processing And Storage ◽  
And Storage ◽  
Hplc Measurement ◽  
Colorimetric Reaction ◽  
Good Agreement

1. Tryptophan losses in stored milk powders and in different model systems representing the major reactions of food proteins during processing and storage were determined using four different chemical methods and in a rat assay.2. Similar tryptophan values were obtained by the three chemical methods which included high pressure liquid chromatography (HPLC) after sodium hydroxide hydrolysis. colorimetric reaction withp-dimethylamino- benzaldehyde (p-DAB) after barium hydroxide hydrolysis, and fluorescence of the Norharman derivative after NaOH hydrolysis.3. Tryptophan losses in the treated proteins as measured by the alkaline-hydrolysis methods were generally smaller than those determined by the rat assay. Good agreement however was obtained when the chemical value was multiplied by the true nitrogen digestibility.4. Determination of tryptophan by reaction withp-DAB after papain (EC 3.4.22.2) digestion gave lower values in the processed proteins than the other chemical methods or the rat assay.5. A method using alkaline-hydrolysis is recommended, preferably combined with HPLC-measurement of the liberated tryptophan.

Pyrraline content in enteral formula processing and storage and model systems

2004 ◽  
Vol 219 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Jos� �ngel Rufi�n-Henares ◽  
Eduardo Guerra-Hern�ndez ◽  
Bel�n Garc�a-Villanova
Keyword(s):  
Model Systems ◽  
Enteral Formula ◽  
Processing And Storage ◽  
And Storage

scholarly journals Heparan Sulfated Glypican-4 is Released from Astrocytes Predominantly by Proteolytic Shedding

2021 ◽  
Author(s):  
Kevin Huang ◽  
Sungjin Park
Keyword(s):  
Synapse Formation ◽  
Regulatory Mechanism ◽  
Active Form ◽  
Release Mechanism ◽  
Loss Of Function ◽  
Secreted Factors ◽  
Release Mechanisms ◽  
Synapse Maturation ◽  
And Function ◽  
Proteolytic Shedding

AbstractAstrocytes provide neurons with diffusible factors that promote synapse formation and maturation. In particular, glypican-4/GPC4 released from astrocytes promotes the maturation of excitatory synapses. Unlike other secreted factors, GPC4 contains the C-terminal GPI-anchorage signal. However, the mechanism by which membrane-tethered GPC4 is released from astrocytes is unknown. Using primary astrocyte cultures and a quantitative luciferase-based release assay, we show that GPC4 is expressed on the astrocyte surface exclusively via a GPI-anchorage. Soluble GPC4 is robustly released from the astrocytes predominantly by proteolytic shedding and, to a lesser extent, by GPI-anchor cleavage, but not by vesicular release. Pharmacological, overexpression, and loss of function screens showed that ADAM9 in part mediates the release of GPC4 from astrocytes. The released GPC4 contains the heparan sulfate side chain, suggesting that these release mechanisms provide the active form that promotes synapse maturation and function. Overall, our studies identified the release mechanisms and the major releasing enzyme of GPC4 in astrocytes and will provide insights into understanding how astrocytes regulate synapse formation and maturation.Significance StatementAstrocyte-derived diffusible factors regulate synapse development and function. However, the regulatory mechanism underlying the release of astrocyte-derived factors is poorly understood. Noting that, unlike many other secreted factors, glypican-4/GPC4 is GPI-anchored, we characterized the release mechanism of GPI-anchored GPC4 from astrocytes and identified the releasing enzyme. Heparan sulfated GPC4 is robustly released from the astrocytes predominantly by proteolytic shedding. In particular, ADAM9 in part mediates the release of GPC4 from astrocytes. Our study provides an enzymatic mechanism for releasing GPC4 from astrocytes and will provide a novel opportunity to understand the regulatory mechanism of neuron-glia communication for synaptogenesis.

scholarly journals The Integrity of the HMR complex is necessary for centromeric binding and reproductive isolation in Drosophila

PLoS Genetics ◽  
2021 ◽  
Vol 17 (8) ◽  
pp. e1009744
Author(s):  
Andrea Lukacs ◽  
Andreas W. Thomae ◽  
Peter Krueger ◽  
Tamas Schauer ◽  
Anuroop V. Venkatasubramani ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Model Systems ◽  
Postzygotic Isolation ◽  
Hybrid Male ◽  
Pure Species ◽  
Hybrid Incompatibility ◽  
Genomic Conflict ◽  
Interspecies Hybrids ◽  
And Function ◽  
Two Hybrid

Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, the molecular mechanisms that result in the lethality of interspecies hybrids are still largely unclear. The genus Drosophila, which contains over 1600 different species, is one of the best characterized model systems to study these questions. We showed in the past that the expression levels of the two hybrid incompatibility factors Hmr and Lhr diverged in the two closely related Drosophila species, D. melanogaster and D. simulans, resulting in an increased level of both proteins in interspecies hybrids. The overexpression of the two proteins also leads to mitotic defects, a misregulation in the expression of transposable elements and decreased fertility in pure species. In this work, we describe a distinct six subunit protein complex containing HMR and LHR and analyse the effect of Hmr mutations on complex integrity and function. Our experiments suggest that HMR needs to bring together components of centromeric and pericentromeric chromatin to fulfil its physiological function and to cause hybrid male lethality.

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