Autophagy, an essential cellular process for maintaining cellular homeostasis and eliminating harmful cytoplasmic objects, involves the de novo formation of double-membraned autophagosomes that engulf and degrade cellular debris, protein aggregates, damaged organelles, and pathogens. Central to this process is the phagophore, which forms from donor membranes rich in lipids synthesized at various cellular sites, including the endoplasmic reticulum (ER), which has emerged as a primary source. The ER-associated omegasomes, characterized by their distinctive omega-shaped structure and accumulation of phosphatidylinositol 3-phosphate (PI3P), play a pivotal role in autophagosome formation. Omegasomes are thought to serve as platforms for phagophore assembly by recruiting essential proteins such as DFCP1/ZFYVE1 and facilitating lipid transfer to expand the phagophore. Despite the critical importance of phagophore biogenesis, many aspects remain poorly understood, particularly the complete range of proteins involved in omegasome dynamics, and the detailed mechanisms of lipid transfer and membrane contact site formation.
{"title":"Omegasomes control formation, expansion, and closure of autophagosomes","authors":"Viola Nähse, Harald Stenmark, Kay O. Schink","doi":"10.1002/bies.202400038","DOIUrl":"10.1002/bies.202400038","url":null,"abstract":"<p>Autophagy, an essential cellular process for maintaining cellular homeostasis and eliminating harmful cytoplasmic objects, involves the de novo formation of double-membraned autophagosomes that engulf and degrade cellular debris, protein aggregates, damaged organelles, and pathogens. Central to this process is the phagophore, which forms from donor membranes rich in lipids synthesized at various cellular sites, including the endoplasmic reticulum (ER), which has emerged as a primary source. The ER-associated omegasomes, characterized by their distinctive omega-shaped structure and accumulation of phosphatidylinositol 3-phosphate (PI3P), play a pivotal role in autophagosome formation. Omegasomes are thought to serve as platforms for phagophore assembly by recruiting essential proteins such as DFCP1/ZFYVE1 and facilitating lipid transfer to expand the phagophore. Despite the critical importance of phagophore biogenesis, many aspects remain poorly understood, particularly the complete range of proteins involved in omegasome dynamics, and the detailed mechanisms of lipid transfer and membrane contact site formation.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202400038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali Salman, Nikita Biziaev, Ekaterina Shuvalova, Elena Alkalaeva
The genetic code is a set of instructions that determine how the information in our genetic material is translated into amino acids. In general, it is universal for all organisms, from viruses and bacteria to humans. However, in the last few decades, exceptions to this rule have been identified both in pro- and eukaryotes. In this review, we discuss the 16 described alternative eukaryotic nuclear genetic codes and observe theories of their appearance in evolution. We consider possible molecular mechanisms that allow codon reassignment. Most reassignments in nuclear genetic codes are observed for stop codons. Moreover, in several organisms, stop codons can simultaneously encode amino acids and serve as termination signals. In this case, the meaning of the codon is determined by the additional factors besides the triplets. A comprehensive review of various non-standard coding events in the nuclear genomes provides a new insight into the translation mechanism in eukaryotes.
{"title":"mRNA context and translation factors determine decoding in alternative nuclear genetic codes","authors":"Ali Salman, Nikita Biziaev, Ekaterina Shuvalova, Elena Alkalaeva","doi":"10.1002/bies.202400058","DOIUrl":"10.1002/bies.202400058","url":null,"abstract":"<p>The genetic code is a set of instructions that determine how the information in our genetic material is translated into amino acids. In general, it is universal for all organisms, from viruses and bacteria to humans. However, in the last few decades, exceptions to this rule have been identified both in pro- and eukaryotes. In this review, we discuss the 16 described alternative eukaryotic nuclear genetic codes and observe theories of their appearance in evolution. We consider possible molecular mechanisms that allow codon reassignment. Most reassignments in nuclear genetic codes are observed for stop codons. Moreover, in several organisms, stop codons can simultaneously encode amino acids and serve as termination signals. In this case, the meaning of the codon is determined by the additional factors besides the triplets. A comprehensive review of various non-standard coding events in the nuclear genomes provides a new insight into the translation mechanism in eukaryotes.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140896255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Camille Moeckel, Ioannis Mouratidis, Nikol Chantzi, Yasin Uzun, Ilias Georgakopoulos-Soares
Understanding the influence of cis-regulatory elements on gene regulation poses numerous challenges given complexities stemming from variations in transcription factor (TF) binding, chromatin accessibility, structural constraints, and cell-type differences. This review discusses the role of gene regulatory networks in enhancing understanding of transcriptional regulation and covers construction methods ranging from expression-based approaches to supervised machine learning. Additionally, key experimental methods, including MPRAs and CRISPR-Cas9-based screening, which have significantly contributed to understanding TF binding preferences and cis-regulatory element functions, are explored. Lastly, the potential of machine learning and artificial intelligence to unravel cis-regulatory logic is analyzed. These computational advances have far-reaching implications for precision medicine, therapeutic target discovery, and the study of genetic variations in health and disease.
{"title":"Advances in computational and experimental approaches for deciphering transcriptional regulatory networks","authors":"Camille Moeckel, Ioannis Mouratidis, Nikol Chantzi, Yasin Uzun, Ilias Georgakopoulos-Soares","doi":"10.1002/bies.202300210","DOIUrl":"10.1002/bies.202300210","url":null,"abstract":"<p>Understanding the influence of <i>cis</i>-regulatory elements on gene regulation poses numerous challenges given complexities stemming from variations in transcription factor (TF) binding, chromatin accessibility, structural constraints, and cell-type differences. This review discusses the role of gene regulatory networks in enhancing understanding of transcriptional regulation and covers construction methods ranging from expression-based approaches to supervised machine learning. Additionally, key experimental methods, including MPRAs and CRISPR-Cas9-based screening, which have significantly contributed to understanding TF binding preferences and cis-regulatory element functions, are explored. Lastly, the potential of machine learning and artificial intelligence to unravel <i>cis</i>-regulatory logic is analyzed. These computational advances have far-reaching implications for precision medicine, therapeutic target discovery, and the study of genetic variations in health and disease.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202300210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sourav Banerjee, Nicola Minshall, Helena Webb, Mark Carrington
Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.
{"title":"How are Trypanosoma brucei receptors protected from host antibody-mediated attack?","authors":"Sourav Banerjee, Nicola Minshall, Helena Webb, Mark Carrington","doi":"10.1002/bies.202400053","DOIUrl":"10.1002/bies.202400053","url":null,"abstract":"<p><i>Trypanosoma brucei</i> is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long-term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, <i>T. brucei</i> acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin-hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent findings on the structure and cell biology of the receptors.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202400053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An indirect perspective to link genetic mosaicism and tumorigenesis","authors":"Leone Albinati, Renée Beekman","doi":"10.1002/bies.202400102","DOIUrl":"10.1002/bies.202400102","url":null,"abstract":"","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.
肌萎缩性脊髓侧索硬化症(ALS)是一种神经退行性疾病,主要导致运动神经元变性。传统的研究重点是以运动神经元为中心的机制,最近已转向了解小胶质细胞等非神经元细胞在 ALS 病理生理学中的作用。诱导多能干细胞(iPSC)技术的进步使人们能够生成 iPSC 衍生的小胶质细胞单培养物和共培养物,以研究它们在 ALS 发病机制中的作用。在此,我们简要回顾了这些研究对小胶质细胞在 ALS 中作用的见解。iPSC 衍生的小胶质细胞单培养物揭示了 ALS 相关突变导致的内在细胞功能障碍,而小胶质细胞-运动神经元共培养研究则证明了突变小胶质细胞对运动神经元的神经毒性作用。基于这些发现,我们简要讨论了目前尚未解决的问题以及如何在未来的研究中解决这些问题。iPSC 模型有望揭示 ALS 的疾病相关通路并确定潜在的治疗靶点。
{"title":"Recent insights from human induced pluripotent stem cell models into the role of microglia in amyotrophic lateral sclerosis","authors":"Lara M. Nikel, Kevin Talbot, Björn F. Vahsen","doi":"10.1002/bies.202400054","DOIUrl":"10.1002/bies.202400054","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron-centric mechanisms has recently shifted towards understanding the contribution of non-neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC-derived microglia monocultures and co-cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of microglia in ALS. While iPSC-derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS-associated mutations, microglia-motor neuron co-culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease-relevant pathways in ALS and identifying potential therapeutic targets.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202400054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This article reflects on sustainability in the context of scientific conferences with emphasis on environmental, diversity, inclusivity, and intellectual aspects. We argue that it is imperative to embrace sustainability as a broad concept during conference organization. In-person conferences have an obvious environmental impact but mitigating strategies can be implemented, such as incentivizing low-emission travel, offering fellowships to support sustainable traveling, and promoting use of public transport or car-pooling. Utilizing eco-conscious venues, catering, and accommodations, along with minimizing resource wastage, further reduces environmental impact. Additional considerations include facilitating hybrid format conferences that allow both in-person and online attendance. Hybrid conferences enhance global participation whilst reducing resource consumption and environmental impact. Often-overlooked benefits can arise from the simple recording of talks to enable asynchronous viewing for people unable to attend in person, in addition to providing a legacy of knowledge that, for example, could support the training of early career researchers (ECRs) or newcomers in the field. The longevity of a research field, intellectual sustainability, requires an inclusive conference atmosphere, offering optimal opportunities for ECRs, minority groups, and researchers from emerging countries. Diversity and inclusivity not only enrich conference experiences but also enhances creativity and innovation.
{"title":"Sustainability in a broad sense: An essential aspect of scientific conferences","authors":"Malene Brohus, Martin D. Bootman, Geert Bultynck","doi":"10.1002/bies.202400017","DOIUrl":"10.1002/bies.202400017","url":null,"abstract":"<p>This article reflects on sustainability in the context of scientific conferences with emphasis on environmental, diversity, inclusivity, and intellectual aspects. We argue that it is imperative to embrace sustainability as a broad concept during conference organization. In-person conferences have an obvious environmental impact but mitigating strategies can be implemented, such as incentivizing low-emission travel, offering fellowships to support sustainable traveling, and promoting use of public transport or car-pooling. Utilizing eco-conscious venues, catering, and accommodations, along with minimizing resource wastage, further reduces environmental impact. Additional considerations include facilitating hybrid format conferences that allow both in-person and online attendance. Hybrid conferences enhance global participation whilst reducing resource consumption and environmental impact. Often-overlooked benefits can arise from the simple recording of talks to enable asynchronous viewing for people unable to attend in person, in addition to providing a legacy of knowledge that, for example, could support the training of early career researchers (ECRs) or newcomers in the field. The longevity of a research field, intellectual sustainability, requires an inclusive conference atmosphere, offering optimal opportunities for ECRs, minority groups, and researchers from emerging countries. Diversity and inclusivity not only enrich conference experiences but also enhances creativity and innovation.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ajay Bhat, Faith R. Carranza, Angela M. Tuckowski, Scott F. Leiser
Flavin-containing monooxygenases (FMOs), traditionally known for detoxifying xenobiotics, are now recognized for their involvement in endogenous metabolism. We recently discovered that an isoform of FMO, fmo-2 in Caenorhabditis elegans, alters endogenous metabolism to impact longevity and stress tolerance. Increased expression of fmo-2 in C. elegans modifies the flux through the key pathway known as One Carbon Metabolism (OCM). This modified flux results in a decrease in the ratio of S-adenosyl-methionine (SAM) to S-adenosyl-homocysteine (SAH), consequently diminishing methylation capacity. Here we discuss how FMO-2-mediated formate production during tryptophan metabolism may serve as a trigger for changing the flux in OCM. We suggest formate bridges tryptophan and OCM, altering metabolic flux away from methylation during fmo-2 overexpression. Additionally, we highlight how these metabolic results intersect with the mTOR and AMPK pathways, in addition to mitochondrial metabolism. In conclusion, the goal of this essay is to bring attention to the central role of FMO enzymes but lack of understanding of their mechanisms. We justify a call for a deeper understanding of FMO enzyme's role in metabolic rewiring through tryptophan/formate or other yet unidentified substrates. Additionally, we emphasize the identification of novel drugs and microbes to induce FMO activity and extend lifespan.
{"title":"Flavin-containing monooxygenase (FMO): Beyond xenobiotics","authors":"Ajay Bhat, Faith R. Carranza, Angela M. Tuckowski, Scott F. Leiser","doi":"10.1002/bies.202400029","DOIUrl":"10.1002/bies.202400029","url":null,"abstract":"<p>Flavin-containing monooxygenases (FMOs), traditionally known for detoxifying xenobiotics, are now recognized for their involvement in endogenous metabolism. We recently discovered that an isoform of FMO, <i>fmo-2</i> in <i>Caenorhabditis elegans</i>, alters endogenous metabolism to impact longevity and stress tolerance. Increased expression of <i>fmo-2</i> in <i>C. elegans</i> modifies the flux through the key pathway known as One Carbon Metabolism (OCM). This modified flux results in a decrease in the ratio of S-adenosyl-methionine (SAM) to S-adenosyl-homocysteine (SAH), consequently diminishing methylation capacity. Here we discuss how FMO-2-mediated formate production during tryptophan metabolism may serve as a trigger for changing the flux in OCM. We suggest formate bridges tryptophan and OCM, altering metabolic flux away from methylation during <i>fmo-2</i> overexpression. Additionally, we highlight how these metabolic results intersect with the mTOR and AMPK pathways, in addition to mitochondrial metabolism. In conclusion, the goal of this essay is to bring attention to the central role of FMO enzymes but lack of understanding of their mechanisms. We justify a call for a deeper understanding of FMO enzyme's role in metabolic rewiring through tryptophan/formate or other yet unidentified substrates. Additionally, we emphasize the identification of novel drugs and microbes to induce FMO activity and extend lifespan.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202400029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stijn Voerman, Robin Broersen, Sigrid M. A. Swagemakers, Chris I. De Zeeuw, Peter J. van der Spek
Despite its uniform appearance, the cerebellar cortex is highly heterogeneous in terms of structure, genetics and physiology. Purkinje cells (PCs), the principal and sole output neurons of the cerebellar cortex, can be categorized into multiple populations that differentially express molecular markers and display distinctive physiological features. Such features include action potential rate, but also their propensity for synaptic and intrinsic plasticity. However, the precise molecular and genetic factors that correlate with the differential physiological properties of PCs remain elusive. In this article, we provide a detailed overview of the cellular mechanisms that regulate PC activity and plasticity. We further perform a pathway analysis to highlight how molecular characteristics of specific PC populations may influence their physiology and plasticity mechanisms.
尽管小脑皮质的外观千篇一律,但它在结构、遗传学和生理学方面却具有高度异质性。小脑皮质的主要和唯一输出神经元浦肯野细胞(PCs)可分为多个种群,这些种群可不同地表达分子标记并显示出独特的生理特征。这些特征包括动作电位率、突触倾向和内在可塑性。然而,与 PCs 不同生理特性相关的确切分子和遗传因素仍然难以捉摸。在本文中,我们将详细概述调控 PC 活性和可塑性的细胞机制。我们还进一步进行了通路分析,以强调特定 PC 群的分子特征可能如何影响其生理学和可塑性机制。
{"title":"Plasticity mechanisms of genetically distinct Purkinje cells","authors":"Stijn Voerman, Robin Broersen, Sigrid M. A. Swagemakers, Chris I. De Zeeuw, Peter J. van der Spek","doi":"10.1002/bies.202400008","DOIUrl":"10.1002/bies.202400008","url":null,"abstract":"<p>Despite its uniform appearance, the cerebellar cortex is highly heterogeneous in terms of structure, genetics and physiology. Purkinje cells (PCs), the principal and sole output neurons of the cerebellar cortex, can be categorized into multiple populations that differentially express molecular markers and display distinctive physiological features. Such features include action potential rate, but also their propensity for synaptic and intrinsic plasticity. However, the precise molecular and genetic factors that correlate with the differential physiological properties of PCs remain elusive. In this article, we provide a detailed overview of the cellular mechanisms that regulate PC activity and plasticity. We further perform a pathway analysis to highlight how molecular characteristics of specific PC populations may influence their physiology and plasticity mechanisms.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202400008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Long-term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A combination of AMPAR structural data, super-resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever-clearer picture of how AMPARs are recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse.
{"title":"Tuning synaptic strength by regulation of AMPA glutamate receptor localization","authors":"Imogen Stockwell, Jake F. Watson, Ingo H. Greger","doi":"10.1002/bies.202400006","DOIUrl":"10.1002/bies.202400006","url":null,"abstract":"<p>Long-term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A combination of AMPAR structural data, super-resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever-clearer picture of how AMPARs are recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse.</p>","PeriodicalId":9264,"journal":{"name":"BioEssays","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bies.202400006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140840842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}