scholarly journals Emerging Concepts and Functions of Autophagy as a Regulator of Synaptic Components and Plasticity

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 34 ◽  
Author(s):  
YongTian Liang
Keyword(s):  
Synaptic Plasticity ◽  
Protein Interactions ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Protein Protein Interactions ◽  
Neuronal Function ◽  
And Function ◽  
Cellular Components ◽  
Neuronal Autophagy

Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity.

scholarly journals Neuron-Derived Estrogen—A Key Neuromodulator in Synaptic Function and Memory

2021 ◽  
Vol 22 (24) ◽  
pp. 13242
Author(s):  
Darrell W. Brann ◽  
Yujiao Lu ◽  
Jing Wang ◽  
Gangadhara R. Sareddy ◽  
Uday P. Pratap ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Knockout Mice ◽  
Long Term Potentiation ◽  
Reference Memory ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Spine Density ◽  
And Function ◽  
The Brain

In addition to being a steroid hormone, 17β-estradiol (E2) is also a neurosteroid produced in neurons in various regions of the brain of many species, including humans. Neuron-derived E2 (NDE2) is synthesized from androgen precursors via the action of the biosynthetic enzyme aromatase, which is located at synapses and in presynaptic terminals in neurons in both the male and female brain. In this review, we discuss evidence supporting a key role for NDE2 as a neuromodulator that regulates synaptic plasticity and memory. Evidence supporting an important neuromodulatory role of NDE2 in the brain has come from studies using aromatase inhibitors, aromatase overexpression in neurons, global aromatase knockout mice, and the recent development of conditional forebrain neuron-specific knockout mice. Collectively, these studies demonstrate a key role of NDE2 in the regulation of synapse and spine density, efficacy of excitatory synaptic transmission and long-term potentiation, and regulation of hippocampal-dependent recognition memory, spatial reference memory, and contextual fear memory. NDE2 is suggested to achieve these effects through estrogen receptor-mediated regulation of rapid kinase signaling and CREB-BDNF signaling pathways, which regulate actin remodeling, as well as transcription, translation, and transport of synaptic proteins critical for synaptic plasticity and function.

scholarly journals GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity

2003 ◽  
Vol 358 (1432) ◽  
pp. 715-720 ◽  
Author(s):  
Fabrice Duprat ◽  
Michael Daw ◽  
Wonil Lim ◽  
Graham Collingridge ◽  
John Isaac
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Protein Interactions ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Synaptic Proteins ◽  
Mammalian Brain ◽  
Protein Protein Interactions ◽  
Term Potentiation

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.

scholarly journals A proline-rich sequence unique to MEK1 and MEK2 is required for raf binding and regulates MEK function.

1995 ◽  
Vol 15 (10) ◽  
pp. 5214-5225 ◽  
Author(s):  
A D Catling ◽  
H J Schaeffer ◽  
C W Reuter ◽  
G R Reddy ◽  
M J Weber
Keyword(s):  
Protein Interactions ◽  
Critical Role ◽  
Phosphorylation Site ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Serum Stimulation ◽  
And Function

Mammalian MEK1 and MEK2 contain a proline-rich (PR) sequence that is absent both from the yeast homologs Ste7 and Byr1 and from a recently cloned activator of the JNK/stress-activated protein kinases, SEK1/MKK4. Since this PR sequence occurs in MEKs that are regulated by Raf family enzymes but is missing from MEKs and SEKs activated independently of Raf, we sought to investigate the role of this sequence in MEK1 and MEK2 regulation and function. Deletion of the PR sequence from MEK1 blocked the ability of MEK1 to associate with members of the Raf family and markedly attenuated activation of the protein in vivo following growth factor stimulation. In addition, this sequence was necessary for efficient activation of MEK1 in vitro by B-Raf but dispensable for activation by a novel MEK1 activator which we have previously detected in fractionated fibroblast extracts. Furthermore, we found that a phosphorylation site within the PR sequence of MEK1 was required for sustained MEK1 activity in response to serum stimulation of quiescent fibroblasts. Consistent with this observation, we observed that MEK2, which lacks a phosphorylation site at the corresponding position, was activated only transiently following serum stimulation. Finally, we found that deletion of the PR sequence from a constitutively activated MEK1 mutant rendered the protein nontransforming in Rat1 fibroblasts. These observations indicate a critical role for the PR sequence in directing specific protein-protein interactions important for the activation, inactivation, and downstream functioning of the MEKs.

scholarly journals The Role of Meningococcal Porin B in Protein-Protein Interactions with Host Cells

2018 ◽  
Vol 62 (1) ◽  
pp. 52-58
Author(s):  
E. Káňová ◽  
I. Jiménez-Munguía ◽  
Ľ. Čomor ◽  
Z. Tkáčová ◽  
I. Širochmanová ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Cell Signalling ◽  
Structure And Function ◽  
Host Cells ◽  
Protein Protein Interactions ◽  
Receptor Interactions ◽  
And Function ◽  
Fatal Sepsis ◽  
Porin B

Abstract Neisseria meningitidis is a Gram-negative diplococcus responsible for bacterial meningitis and fatal sepsis. Ligand-receptor interactions are one of the main steps in the development of neuroinvasion. Porin B (PorB), neisserial outer membrane protein (ligand), binds to host receptors and triggers many cell signalling cascades allowing the meningococcus to damage the host cells or induce immune cells responses via the TLR2-dependent mechanisms. In this paper, we present a brief review of the structure and function of PorB.

scholarly journals Role of MicroRNA in Governing Synaptic Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Yuqin Ye ◽  
Hongyu Xu ◽  
Xinhong Su ◽  
Xiaosheng He
Keyword(s):  
Synaptic Plasticity ◽  
Neurological Disorders ◽  
Therapeutic Strategy ◽  
Target Gene ◽  
Synaptic Function ◽  
The Novel ◽  
Individual Mirnas ◽  
Underlying Mechanisms ◽  
And Function

Although synaptic plasticity in neural circuits is orchestrated by an ocean of genes, molecules, and proteins, the underlying mechanisms remain poorly understood. Recently, it is well acknowledged that miRNA exerts widespread regulation over the translation and degradation of target gene in nervous system. Increasing evidence suggests that quite a few specific miRNAs play important roles in various respects of synaptic plasticity including synaptogenesis, synaptic morphology alteration, and synaptic function modification. More importantly, the miRNA-mediated regulation of synaptic plasticity is not only responsible for synapse development and function but also involved in the pathophysiology of plasticity-related diseases. A review is made here on the function of miRNAs in governing synaptic plasticity, emphasizing the emerging regulatory role of individual miRNAs in synaptic morphological and functional plasticity, as well as their implications in neurological disorders. Understanding of the way in which miRNAs contribute to synaptic plasticity provides rational clues in establishing the novel therapeutic strategy for plasticity-related diseases.

scholarly journals Synaptic Function and Dysfunction in Lysosomal Storage Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
Rima Rebiai ◽  
Maria I. Givogri ◽  
Swetha Gowrishankar ◽  
Stephania M. Cologna ◽  
Simon T. Alford ◽  
...  
Keyword(s):  
Cognitive Deficits ◽  
Genetic Diseases ◽  
Lysosomal Storage Diseases ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Neurological Involvement ◽  
Lysosomal Storage ◽  
Neuronal Function ◽  
Storage Diseases ◽  
And Function

Lysosomal storage diseases (LSDs) with neurological involvement are inherited genetic diseases of the metabolism characterized by lysosomal dysfunction and the accumulation of undegraded substrates altering glial and neuronal function. Often, patients with neurological manifestations present with damage to the gray and white matter and irreversible neuronal decline. The use of animal models of LSDs has greatly facilitated studying and identifying potential mechanisms of neuronal dysfunction, including alterations in availability and function of synaptic proteins, modifications of membrane structure, deficits in docking, exocytosis, recycling of synaptic vesicles, and inflammation-mediated remodeling of synapses. Although some extrapolations from findings in adult-onset conditions such as Alzheimer’s disease or Parkinson’s disease have been reported, the pathogenetic mechanisms underpinning cognitive deficits in LSDs are still largely unclear. Without being fully inclusive, the goal of this mini-review is to present a discussion on possible mechanisms leading to synaptic dysfunction in LSDs.

scholarly journals The Role of Low Complexity Regions in Protein Interaction Modes: An Illustration in Huntingtin

2021 ◽  
Vol 22 (4) ◽  
pp. 1727
Author(s):  
Kristina Kastano ◽  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Structural Information ◽  
Low Complexity ◽  
Protein Interaction Data ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Evolutionarily Conserved ◽  
And Function

Low complexity regions (LCRs) are very frequent in protein sequences, generally having a lower propensity to form structured domains and tending to be much less evolutionarily conserved than globular domains. Their higher abundance in eukaryotes and in species with more cellular types agrees with a growing number of reports on their function in protein interactions regulated by post-translational modifications. LCRs facilitate the increase of regulatory and network complexity required with the emergence of organisms with more complex tissue distribution and development. Although the low conservation and structural flexibility of LCRs complicate their study, evolutionary studies of proteins across species have been used to evaluate their significance and function. To investigate how to apply this evolutionary approach to the study of LCR function in protein–protein interactions, we performed a detailed analysis for Huntingtin (HTT), a large protein that is a hub for interaction with hundreds of proteins, has a variety of LCRs, and for which partial structural information (in complex with HAP40) is available. We hypothesize that proteins RASA1, SYN2, and KAT2B may compete with HAP40 for their attachment to the core of HTT using similar LCRs. Our results illustrate how evolution might favor the interplay of LCRs with domains, and the possibility of detecting multiple modes of LCR-mediated protein–protein interactions with a large hub such as HTT when enough protein interaction data is available.

scholarly journals The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Wallace H Liu ◽  
Sarah C Roemer ◽  
Yeyun Zhou ◽  
Zih-Jie Shen ◽  
Briana K Dennehey ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Histone Chaperone ◽  
Protein Protein Interactions ◽  
Rich Domain ◽  
C Terminus ◽  
Assembly Factor ◽  
Hydrogen Deuterium ◽  
And Function ◽  
Minimal Region

The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone not only binds H3/H4 with high affinity, but also promotes histone tetramerization independent of the other subunits. Moreover, we identify a minimal region in the C-terminus of Cac1, including the structured winged helix domain and glutamate/aspartate-rich domain, which is sufficient to induce (H3/H4)2 tetramerization. These findings reveal a key role of Cac1 in histone tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic replication.

scholarly journals Interactome Analysis of KIN (Kin17) Shows New Functions of This Protein

2021 ◽  
Vol 43 (2) ◽  
pp. 767-781
Author(s):  
Vanessa Pinatto Gaspar ◽  
Anelise Cardoso Ramos ◽  
Philippe Cloutier ◽  
José Renato Pattaro Junior ◽  
Francisco Ferreira Duarte Junior ◽  
...  
Keyword(s):  
Dna Replication ◽  
Protein Interactions ◽  
Ribosome Biogenesis ◽  
Cell Metabolism ◽  
Cell Types ◽  
Protein Protein Interactions ◽  
Cellular Mechanisms ◽  
Cancerous Cell ◽  
First Time

KIN (Kin17) protein is overexpressed in a number of cancerous cell lines, and is therefore considered a possible cancer biomarker. It is a well-conserved protein across eukaryotes and is ubiquitously expressed in all cell types studied, suggesting an important role in the maintenance of basic cellular function which is yet to be well determined. Early studies on KIN suggested that this nuclear protein plays a role in cellular mechanisms such as DNA replication and/or repair; however, its association with chromatin depends on its methylation state. In order to provide a better understanding of the cellular role of this protein, we investigated its interactome by proximity-dependent biotin identification coupled to mass spectrometry (BioID-MS), used for identification of protein–protein interactions. Our analyses detected interaction with a novel set of proteins and reinforced previous observations linking KIN to factors involved in RNA processing, notably pre-mRNA splicing and ribosome biogenesis. However, little evidence supports that this protein is directly coupled to DNA replication and/or repair processes, as previously suggested. Furthermore, a novel interaction was observed with PRMT7 (protein arginine methyltransferase 7) and we demonstrated that KIN is modified by this enzyme. This interactome analysis indicates that KIN is associated with several cell metabolism functions, and shows for the first time an association with ribosome biogenesis, suggesting that KIN is likely a moonlight protein.

scholarly journals A unified resource and configurable model of the synapse proteome and its role in disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Oksana Sorokina ◽  
Colin Mclean ◽  
Mike D. R. Croning ◽  
Katharina F. Heil ◽  
Emilia Wysocka ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Synaptic Proteins ◽  
Protein Protein Interactions ◽  
Network Resource ◽  
Unique Protein ◽  
Co Morbidity ◽  
Genes Encoding ◽  
Protein Components ◽  
Accessible Format ◽  
Neuronal Disorders

AbstractGenes encoding synaptic proteins are highly associated with neuronal disorders many of which show clinical co-morbidity. We integrated 58 published synaptic proteomic datasets that describe over 8000 proteins and combined them with direct protein–protein interactions and functional metadata to build a network resource that reveals the shared and unique protein components that underpin multiple disorders. All the data are provided in a flexible and accessible format to encourage custom use.

Sign in / Sign up

Export Citation Format

Share Document