scholarly journals Evolutionarily Established Palmitoylation-Dependent Regulatory Mechanisms of the Vertebrate Glutamatergic Synapse and Diseases Caused by Their Disruption

2021 ◽  
Vol 14 ◽  
Author(s):  
Takashi Hayashi
Keyword(s):  
Receptor Binding ◽  
Protein Modification ◽  
Recent Progress ◽  
Synaptic Proteins ◽  
Regulatory Mechanisms ◽  
Evolutionary Development ◽  
Glutamatergic Synapse ◽  
Glutamatergic Synapses ◽  
Excitatory Neurotransmitter ◽  
Vertebrate Brain

Glutamate is the major excitatory neurotransmitter in the vertebrate brain and various modifications have been established in the glutamatergic synapses. Generally, many neuronal receptors and ion channels are regulated by S-palmitoylation, a reversible post-translational protein modification. Genome sequence databases show the evolutionary acquisition and conservation concerning vertebrate-specific palmitoylation of synaptic proteins including glutamate receptors. Moreover, palmitoylation of some glutamate receptor-binding proteins is subsequently acquired only in some mammalian lineages. Recent progress in genome studies has revealed that some palmitoylation-catalyzing enzymes are the causative genes of neuropsychiatric disorders. In this review, I will summarize the evolutionary development of palmitoylation-dependent regulation of glutamatergic synapses and their dysfunctions which are caused by the disruption of palmitoylation mechanism.

scholarly journals Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation

2017 ◽  
Vol 114 (4) ◽  
pp. E610-E618 ◽  
Author(s):  
Sonal Thakar ◽  
Liqing Wang ◽  
Ting Yu ◽  
Mao Ye ◽  
Keisuke Onishi ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Conditional Knockout ◽  
Synaptic Proteins ◽  
Inhibitory Synapses ◽  
Spatial Learning And Memory ◽  
Spine Density ◽  
Glutamatergic Synapse ◽  
Glutamatergic Synapses ◽  
Core Components

The signaling mechanisms that choreograph the assembly of the highly asymmetric pre- and postsynaptic structures are still poorly defined. Using synaptosome fractionation, immunostaining, and coimmunoprecipitation, we found that Celsr3 and Vangl2, core components of the planar cell polarity (PCP) pathway, are localized at developing glutamatergic synapses and interact with key synaptic proteins. Pyramidal neurons from the hippocampus of Celsr3 knockout mice exhibit loss of ∼50% of glutamatergic synapses, but not inhibitory synapses, in culture. Wnts are known regulators of synapse formation, and our data reveal that Wnt5a inhibits glutamatergic synapses formed via Celsr3. To avoid affecting earlier developmental processes, such as axon guidance, we conditionally knocked out Celsr3 in the hippocampus 1 week after birth. The CA1 neurons that lost Celsr3 also showed a loss of ∼50% of glutamatergic synapses in vivo without affecting the inhibitory synapses assessed by miniature excitatory postsynaptic current (mEPSC) and electron microscopy. These animals displayed deficits in hippocampus-dependent behaviors in adulthood, including spatial learning and memory and fear conditioning. In contrast to Celsr3 conditional knockouts, we found that the conditional knockout of Vangl2 in the hippocampus 1 week after birth led to a large increase in synaptic density, as evaluated by mEPSC frequency and spine density. PCP signaling is mediated by multiple core components with antagonizing functions. Our results document the opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation.

The Modification and Design of Antimicrobial Peptide

2018 ◽  
Vol 24 (8) ◽  
pp. 904-910 ◽  
Author(s):  
Yidan Gao ◽  
Hengtong Fang ◽  
Lu Fang ◽  
Dawei Liu ◽  
Jinsong Liu ◽  
...  
Keyword(s):  
Chemical Modification ◽  
Antimicrobial Peptide ◽  
Protein Modification ◽  
Recent Progress ◽  
Therapeutic Agents ◽  
Manufacturing Cost ◽  
Commercial Development ◽  
Biochemical Modification ◽  
Naturally Occurring ◽  
Application Prospects

The antimicrobial peptides (AMPs) are a group of unique naturally occurring anti-microbial compounds with around 50 amino acids. It represents promising therapeutic agents to the infectious disease without concerning about drug resistance. However, commercial development of these peptides for even the simplest application has been hindered by the limitations of sources, instability, toxicity and bioavailability. To improve the properties of the artificial synthesized AMPs, the modification and design are the hotspots of the AMPs research. In fact, more than half of the known AMPs are naturally modified. In this review, two types of modification strategies, biochemical modification and chemical modification were summarized. Although, the chemical modification is versatile and direct, the manufacturing cost is greatly increased compared to the antibiotics. With the recent progress of the protein modification enzyme, the biochemical modification of the antimicrobial peptide followed by heterologous expression has great application prospects.

scholarly journals The Impact of Oxytocin on Neurite Outgrowth and Synaptic Proteins in Magel2-Deficient Mice

2020 ◽  
Author(s):  
Alexandra Reichova ◽  
Fabienne Schaller ◽  
Stanislava Bukatova ◽  
Zuzana Bacova ◽  
Françoise Muscatelli ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Hippocampal Neurons ◽  
Synapse Formation ◽  
Primary Cultures ◽  
Synaptic Proteins ◽  
Neuronal Maturation ◽  
Glutamatergic Synapses ◽  
Associated Proteins ◽  
The Impact ◽  
Deficient Mice

AbstractOxytocin contributes to the regulation of cytoskeletal and synaptic proteins and could therefore affect the mechanisms of neurodevelopmental disorders, including autism. Both the Prader-Willi syndrome and Schaaf-Yang syndrome exhibit autistic symptoms involving the MAGEL2 gene. Magel2-deficient mice show a deficit in social behavior that is rescued following postnatal administration of oxytocin. Here, in Magel2-deficient mice, we showed that the neurite outgrowth of primary cultures of immature hippocampal neurons is reduced. Treatment with oxytocin, but not retinoic acid, reversed this abnormality. In the hippocampus of Magel2-deficient pups, we further demonstrated that several transcripts of neurite outgrowth-associated proteins, synaptic vesicle proteins, and cell-adhesion molecules are decreased. In the juvenile stage, when neurons are mature, normalization or even overexpression of most of these markers was observed, suggesting a delay in the neuronal maturation of Magel2-deficient pups. Moreover, we found reduced transcripts of the excitatory postsynaptic marker, Psd95 in the hippocampus and we observed a decrease of PSD95/VGLUT2 colocalization in the hippocampal CA1 and CA3 regions in Magel2-deficient mice, indicating a defect in glutamatergic synapses. Postnatal administration of oxytocin upregulated postsynaptic transcripts in pups; however, it did not restore the level of markers of glutamatergic synapses in Magel2-deficient mice. Overall, Magel2 deficiency leads to abnormal neurite outgrowth and reduced glutamatergic synapses during development, suggesting abnormal neuronal maturation. Oxytocin stimulates the expression of numerous genes involved in neurite outgrowth and synapse formation in early development stages. Postnatal oxytocin administration has a strong effect in development that should be considered for certain neuropsychiatric conditions in infancy.

scholarly journals SUMO modification in apoptosis

2020 ◽  
Vol 52 (1) ◽  
pp. 1-10
Author(s):  
Peiyao Li ◽  
Huiru Jing ◽  
Yanzhe Wang ◽  
Lei Yuan ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Neurodegenerative Diseases ◽  
Growth And Development ◽  
Recent Progress ◽  
Biological Process ◽  
Regulatory Mechanisms ◽  
Apoptotic Cells ◽  
Post Translational Modification ◽  
Sumo Modification ◽  
Evolutionarily Conserved

AbstractApoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular organism. Fail to remove apoptotic cells often lead to homeostasis imbalance, fatal autoimmune diseases, and neurodegenerative diseases. Small ubiquitin-related modifiers (SUMOs) modification is a post-translational modification of ubiquitin proteins mediated by the sentrin-specific proteases (SENPs) family. SUMO modification is widely involved in many cellular biological process, and abnormal SUMO modification is also closely related to many major human diseases. Recent researches have revealed that SUMO modification event occurs during apoptosis and clearance of apoptotic cells, and plays an important role in the regulation of apoptotic signaling pathways. This review summarizes some recent progress in the revelation of regulatory mechanisms of these pathways and provides some potential researching hotpots of the SUMO modification regulation to apoptosis.

Ultrastructural immunocytochemical Synapse Changes In A Rat Model Of Parkinson’s Disease

1999 ◽  
Vol 5 (S2) ◽  
pp. 1230-1231
Author(s):  
C.K. Meshul ◽  
C. Allen ◽  
T. S. Kay
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopamine Neurons ◽  
Current Therapy ◽  
Nerve Terminals ◽  
Glutamatergic Synapses ◽  
Excitatory Neurotransmitter ◽  
Neurotransmitter Glutamate ◽  
Progressive Disorder ◽  
The Brain

Parkinson's disease is a progressive disorder that is characterized by degeneration of the dopamine containing neurons located within the midbrain (substantia nigra). There is also substantial loss of dopamine within nerve terminals located within the striatum which originate from those dopamine neurons. Current therapy involves administration of the precursor to dopamine, namely l-dopa. This chemical is taken up into the brain and then converted to dopamine. Although replacement of dopamine is effective over the first few years, other movement disorders are associated with longterm l-dopa therapy. The l-dopa induced dyskinesias limit the usefulness of this type of therapy.Although loss of dopamine is the major neurochemical deficit in Parkinson's disease, other neurotransmitters within the striatum may also be altered. There is a major axonal projection from the cortex to the striatum. The corticostriatal pathway uses the excitatory neurotransmitter, glutamate, and dopamine is known to modulate the activity of glutamatergic synapses

scholarly journals Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Felipe J. Bodaleo ◽  
Carolina Montenegro-Venegas ◽  
Daniel R. Henríquez ◽  
Felipe A. Court ◽  
Christian Gonzalez-Billault
Keyword(s):  
Axonal Guidance ◽  
Synaptic Proteins ◽  
Glutamatergic Synapses ◽  
Presynaptic Terminals ◽  
Synaptic Contacts ◽  
Mature Neurons ◽  
Release Assay ◽  
Synaptic Vesicle Fusion ◽  
The Brain

Abstract Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro.

scholarly journals Light induced synaptic vesicle autophagy

2018 ◽  
Author(s):  
Sheila Hoffmann ◽  
Marta Orlando ◽  
Ewa Andrzejak ◽  
Thorsten Trimbuch ◽  
Christian Rosenmund ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Real Time ◽  
Hippocampal Neurons ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Oxygen Species ◽  
Local Damage ◽  
Glutamatergic Synapses ◽  
Presynaptic Boutons ◽  
Presynaptic Proteins

AbstractThe regulated turnover of synaptic vesicle (SV) proteins is thought to involve the ubiquitin dependent tagging and degradation through endo-lysosomal and autophagy pathways. Yet, it remains unclear which of these pathways are used, when they become activated and whether SVs are cleared en-mass together with SV proteins or whether both are degraded selectively. Equally puzzling is how quickly these systems can be activated and whether they function in real time to support synaptic health. To address these questions, we have developed an imaging based system that simultaneously tags presynaptic proteins while monitoring autophagy. Moreover, by tagging SV proteins with a light activated reactive oxygen species (ROS) generator, Supernova, it was possible to temporally control the damage to specific SV proteins and assess their consequence to autophagy mediated clearance mechanisms and synaptic function. Our results show that, in mouse hippocampal neurons, presynaptic autophagy can be induced in as little as 5-10 minutes and eliminates primarily the damaged protein rather than the SV en-mass. Importantly, we also find that autophagy is essential for synaptic function, as light-induced damage to e.g. Synaptophysin only compromises synaptic function when autophagy is simultaneously blocked. These data support the concept that presynaptic boutons have a robust highly regulated clearance system to maintain not only synapse integrity, but also synaptic function.Significance StatementThe real-time surveillance and clearance of synaptic proteins is thought to be vital to the health, functionality and integrity of vertebrate synapses and is compromised in neurodegenerative disorders, yet the fundamental mechanisms regulating these systems remain enigmatic. Our analysis reveals that presynaptic autophagy is a critical part of a real-time clearance system at glutamatergic synapses capable of responding to local damage of synaptic vesicle proteins within minutes and to be critical for the ongoing functionality of these synapses. These data indicate that synapse autophagy is not only locally regulated but also crucial for the health and functionality of vertebrate presynaptic boutons.

scholarly journals The evolutionary development of plant body plans

2009 ◽  
Vol 36 (8) ◽  
pp. 682 ◽  
Author(s):  
Karl J. Niklas ◽  
Ulrich Kutschera
Keyword(s):  
Gene Networks ◽  
Functional Divergence ◽  
Evolutionary Developmental Biology ◽  
The Body ◽  
Regulatory Mechanisms ◽  
Evolutionary Development ◽  
Evolutionary Divergence ◽  
Early Maturation ◽  
Photosynthetic Eukaryotes ◽  
Cladistic Analyses

Evolutionary developmental biology, cladistic analyses, and paleontological insights make it increasingly clear that regulatory mechanisms operating during embryogenesis and early maturation tend to be highly conserved over great evolutionary time scales, which can account for the conservative nature of the body plans in the major plant and animal clades. At issue is whether morphological convergences in body plans among evolutionarily divergent lineages are the result of adaptive convergence or ‘genome recall’ and ‘process orthology’. The body plans of multicellular photosynthetic eukaryotes (‘plants’) are reviewed, some of their important developmental/physiological regulatory mechanisms discussed, and the evidence that some of these mechanisms are phyletically ancient examined. We conclude that endosymbiotic lateral gene transfers, gene duplication and functional divergence, and the co-option of ancient gene networks were key to the evolutionary divergence of plant lineages.

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