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Nature Reviews. Molecular Cell Biology Jul 2021Fine-tuning cellular physiology in response to intracellular and environmental cues requires precise temporal and spatial control of gene expression. High-resolution... (Review)
Review
Fine-tuning cellular physiology in response to intracellular and environmental cues requires precise temporal and spatial control of gene expression. High-resolution imaging technologies to detect mRNAs and their translation state have revealed that all living organisms localize mRNAs in subcellular compartments and create translation hotspots, enabling cells to tune gene expression locally. Therefore, mRNA localization is a conserved and integral part of gene expression regulation from prokaryotic to eukaryotic cells. In this Review, we discuss the mechanisms of mRNA transport and local mRNA translation across the kingdoms of life and at organellar, subcellular and multicellular resolution. We also discuss the properties of messenger ribonucleoprotein and higher order RNA granules and how they may influence mRNA transport and local protein synthesis. Finally, we summarize the technological developments that allow us to study mRNA localization and local translation through the simultaneous detection of mRNAs and proteins in single cells, mRNA and nascent protein single-molecule imaging, and bulk RNA and protein detection methods.
Topics: Animals; Cytoplasmic Granules; Gene Expression Regulation; Humans; Protein Biosynthesis; RNA Transport; RNA, Messenger; Ribonucleoproteins
PubMed: 33837370
DOI: 10.1038/s41580-021-00356-8 -
International Journal of Molecular... Apr 2017The pathogenesis-related 1 (PR1) is an important defense protein, so far it has only been detected in extracellular space and its subcellular sorting and transport...
The pathogenesis-related 1 (PR1) is an important defense protein, so far it has only been detected in extracellular space and its subcellular sorting and transport remain unexplained. Using a green fluorescent protein (GFP) tagged full length, as well as a C-terminus truncated version of PR1, we observed that when expressed ectopically in leaves, PR1 co-localizes only partially with Golgi markers, and much more prominently with the late endosome (LE)/multivesicular body (MVB) FYVE marker. The C-truncated version PR1ΔC predominantly localized to the endoplasmic reticulum (ER). The same localizations were found for stable transformants with expression of PR1 and PR1ΔC driven by the native promoter. We conclude that the PR1 (AtPR1) undergoes an unconventional secretion pathway, starting from the C-terminus-dependent sorting from the ER, and utilizing further transportation via phosphatidyl-inositol-3-phosphate (PI(3)P) positive LE/MVB-like vesicles. The homology model of the PR1 structure shows that the cluster of positively charged amino acid residues (arginines 60, 67, 137, and lysine 135) could indeed interact with negatively charged phospholipids of cellular membranes. It remains to be resolved whether Golgi and LE/MVB localization reflects an alternative sorting or trafficking succession, and what the role of lipid interactions in it will be.
Topics: Arabidopsis; Arabidopsis Proteins; Endoplasmic Reticulum; Endosomes; Golgi Apparatus; Green Fluorescent Proteins; Microscopy, Confocal; Phosphatidylinositol Phosphates; Plant Leaves; Promoter Regions, Genetic; Recombinant Fusion Proteins; Nicotiana
PubMed: 28406455
DOI: 10.3390/ijms18040825 -
Epilepsy & Behavior Case Reports 2017To investigate the probable ictal origin of unexplained episodic chest pain and if possible to lateralize and localize the epileptic focus.
PURPOSE
To investigate the probable ictal origin of unexplained episodic chest pain and if possible to lateralize and localize the epileptic focus.
METHODS
A 14 year old boy presented with episodic short lasting localized chest pain. His cardiac and other systemic work-up were normal. MRI brain did not reveal any structural pathology. Video telemetry was done for characterization of the paroxysms.
RESULTS
Interictal record showed left fronto-central epileptiform discharges. A left hemispheric, predominantly centroparietal ictal rhythm was identified. The possible localizations of this unusual semiology are somatosensory areas I and II, supplementary sensorimotor area, posterior insula and cingulate cortex. Patient responded remarkably to antiseizure drugs.
CONCLUSION
Pain is a rare manifestation of epilepsy observed in less than 1% of patients. When present, it is usually accompanied by other focal features. This rare occurrence of epileptic seizures masquerading as angina is a novel observation.
PubMed: 28393015
DOI: 10.1016/j.ebcr.2017.02.001 -
American Journal of Neurodegenerative... 2021The prevalence of neurodegenerative diseases is accelerating in rapidly aging global population. Novel and effective diagnostic and therapeutic methods are required to... (Review)
Review
The prevalence of neurodegenerative diseases is accelerating in rapidly aging global population. Novel and effective diagnostic and therapeutic methods are required to tackle the global issue of neurodegeneration in the future. A better understanding of the potential molecular mechanism causing neurodegeneration can shed light on dysfunctional processes in diseased neurons, which can pave the way to design and synthesize novel targets for early diagnosis during the asymptomatic phase of the disease. Abnormal protein aggregation is a hallmark of neurodegenerative diseases which can hamper transportation of cargoes into axons. Recent evidence suggests that disruption of local protein synthesis has been observed in neurodegenerative diseases. Because of their highly asymmetric structure, highly polarized neurons require trafficking of cargoes from the cell body to different subcellular regions to meet the extensive demands of cellular physiology. Localization of mRNAs and subsequent local translation to corresponding proteins in axons is a mechanism which allows neurons to rapidly respond to external stimuli as well as establishing neuronal networks by synthesizing proteins on demand. Axonal protein synthesis is required for axon guidance, synapse formation and plasticity, axon maintenance and regeneration in response to injury. Different types of excitatory and inhibitory neurons in the central and peripheral nervous systems have been shown to localize mRNA. Rising evidence suggests that the repertoire of localizing mRNA in axons can change during aging, indicating a connection between axonal mRNA trafficking and aging diseases such as neurodegeneration. Here, I briefly review the latest findings on the importance of mRNA localization and local translation in neurons and the consequences of their disruption in neurodegenerative diseases. In addition, I discuss recent evidence that dysregulation of mRNA localization and local protein translation can contribute to the formation of neurodegenerative diseases such as Alzheimer's disease, Amyotrophic Lateral Sclerosis, and Spinal Muscular Atrophy. In addition, I discuss recent findings on mRNAs localizing to mitochondria in neurodegeneration.
PubMed: 33815964
DOI: No ID Found -
Frontiers in Integrative Neuroscience 2021Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for... (Review)
Review
Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for an accurate function of dendrites and axons the neuronal proteome needs to be asymmetrically distributed within neurons. Protein asymmetry can be achieved by the transport of the protein itself or the transport of the mRNA that is then translated at target sites in neuronal processes. The latter transport mechanism implies local translation of localized mRNAs. The role of local translation in nervous system (NS) development and maintenance is well established, but recently there is growing evidence that this mechanism and its deregulation are also relevant in NS pathologies, including neurodegenerative diseases. For instance, upon pathological signals disease-related proteins can be locally synthesized in dendrites and axons. Locally synthesized proteins can exert their effects at or close to the site of translation, or they can be delivered to distal compartments like the nucleus and induce transcriptional responses that lead to neurodegeneration, nerve regeneration and other cell-wide responses. Relevant key players in the process of local protein synthesis are RNA binding proteins (RBPs), responsible for mRNA transport to neurites. Several neurological and neurodegenerative disorders, including amyotrophic lateral sclerosis or spinal motor atrophy, are characterized by mutations in genes encoding for RBPs and consequently mRNA localization and local translation are impaired. In other diseases changes in the local mRNA repertoire and altered local protein synthesis have been reported. In this review, we will discuss how deregulation of localized translation at different levels can contribute to the development and progression of nervous system pathologies.
PubMed: 34276318
DOI: 10.3389/fnint.2021.689208 -
Frontiers in Cell and Developmental... 2021Centrosomes are multifunctional organelles tasked with organizing the microtubule cytoskeleton required for genome stability, intracellular trafficking, and... (Review)
Review
Centrosomes are multifunctional organelles tasked with organizing the microtubule cytoskeleton required for genome stability, intracellular trafficking, and ciliogenesis. Contributing to the diversity of centrosome functions are cell cycle-dependent oscillations in protein localization and post-translational modifications. Less understood is the role of centrosome-localized messenger RNA (mRNA). Since its discovery, the concept of nucleic acids at the centrosome was controversial, and physiological roles for centrosomal mRNAs remained muddled and underexplored. Over the past decades, however, transcripts, RNA-binding proteins, and ribosomes were detected at the centrosome in various organisms and cell types, hinting at a conservation of function. Indeed, recent work defines centrosomes as sites of local protein synthesis, and defined mRNAs were recently implicated in regulating centrosome functions. In this review, we summarize the evidence for the presence of mRNA at the centrosome and the current work that aims to unravel the biological functions of mRNA localized to centrosomes.
PubMed: 34805187
DOI: 10.3389/fcell.2021.782802 -
Science Advances Jul 2022pH controls a large repertoire of chemical and biochemical processes in water. Densely arrayed pH microenvironments would parallelize these processes, enabling their...
pH controls a large repertoire of chemical and biochemical processes in water. Densely arrayed pH microenvironments would parallelize these processes, enabling their high-throughput studies and applications. However, pH localization, let alone its arrayed realization, remains challenging because of fast diffusion of protons in water. Here, we demonstrate arrayed localizations of picoliter-scale aqueous acids, using a 256-electrochemical cell array defined on and operated by a complementary metal oxide semiconductor (CMOS)-integrated circuit. Each cell, comprising a concentric pair of cathode and anode with their current injections controlled with a sub-nanoampere resolution by the CMOS electronics, creates a local pH environment, or a pH "voxel," via confined electrochemistry. The system also monitors the spatiotemporal pH profile across the array in real time for precision pH control. We highlight the utility of this CMOS pH localizer-imager for high-throughput tasks by parallelizing pH-gated molecular state encoding and pH-regulated enzymatic DNA elongation at any selected set of cells.
PubMed: 35895813
DOI: 10.1126/sciadv.abm6815 -
ENeuro Oct 2023Intracranial electroencephalography (iEEG) provides a unique opportunity to record and stimulate neuronal populations in the human brain. A key step in neuroscience...
Intracranial electroencephalography (iEEG) provides a unique opportunity to record and stimulate neuronal populations in the human brain. A key step in neuroscience inference from iEEG is localizing the electrodes relative to individual subject anatomy and identified regions in brain atlases. We describe a new software tool, Your Advanced Electrode Localizer (YAEL), that provides an integrated solution for every step of the electrode localization process. YAEL is compatible with all common data formats to provide an easy-to-use, drop-in replacement for problematic existing workflows that require users to grapple with multiple programs and interfaces. YAEL's automatic extrapolation and interpolation functions speed localization, especially important in patients with many implanted stereotactic (sEEG) electrode shafts. The graphical user interface is presented in a web browser for broad compatibility and includes an interactive 3D viewer for easier localization of nearby sEEG contacts. After localization is complete, users may enter or import data into YAEL's 3D viewer to create publication-ready visualizations of electrodes and brain anatomy, including identified brain areas from atlases; the response to experimental tasks measured with iEEG; and clinical measures such as epileptiform activity or the results of electrical stimulation mapping. YAEL is free and open source and does not depend on any commercial software. Installation instructions for Mac, Windows, and Linux are available at https://yael.wiki.
Topics: Humans; Electroencephalography; Electrocorticography; Brain; Brain Mapping; Electrodes, Implanted
PubMed: 37857509
DOI: 10.1523/ENEURO.0328-23.2023 -
Acta Clinica Croatica Dec 2021Posterior cortex seizures have a complex semiologic presentation that is especially challenging in the pediatric population. Therefore, using clinical presentation in... (Review)
Review
Posterior cortex seizures have a complex semiologic presentation that is especially challenging in the pediatric population. Therefore, using clinical presentation in localizing ictal involvement is not sufficient in children, thus making this type of epilepsy quite under-recognized. As most of the ictal symptoms are subjective and could well be overshadowed by symptoms arising from adjacent cortices, primarily temporal and central ones, it is necessary not to overlook this large source of pharmacoresistant epilepsies. The parietal lobe as part of an extensive synaptic network is a great imitator, thus quite often producing inaccurate localization readings on scalp electroencephalography (EEG) due to very scattered interictal discharges and uninformative ictal recordings. Using direct cortical recordings in delineating the epileptogenic zone is helpful in some cases but even highly experienced epileptologists may erroneously interpret some features as arising from other localizations, especially the frontal lobe. Epilepsy surgery from the posterior quadrant is still quite rare and relatively unsuccessful, especially in non-lesional epilepsies due to elaborate mechanisms of connectivity, misleading semiology, and non-localizing EEG recordings, possibly due to insufficiency of parietal cortex synchronicity. Applying the aforementioned to the pediatric age makes it perhaps the most difficult challenge for a pediatric epileptologist.
Topics: Humans; Child; Electroencephalography; Seizures; Frontal Lobe; Epilepsy; Scalp
PubMed: 36405000
DOI: 10.20471/acc.2021.60.s3.03 -
Journal of Cancer Research and... Sep 2020Along with increasing incidence of operable small pulmonary nodules, it becomes difficult to localize nodules via palpation. Accurate localization of small pulmonary... (Review)
Review
Along with increasing incidence of operable small pulmonary nodules, it becomes difficult to localize nodules via palpation. Accurate localization of small pulmonary nodules has remained a big challenge in lung surgery. Therefore, several techniques for preoperative localizing small pulmonary nodules have evolved, but the advantages and disadvantages of each method remain unclear. We reviewed computed tomography-guided percutaneous and bronchoscopic preoperative assisted localization for small pulmonary nodules. Original, peer-reviewed, and full-length articles in English and Chinese were searched with PubMed and Wanfang data. Case reports and case series with <20 patients were excluded. All localization techniques showed good reliability, but some carry a high rate of major or minor complications and drawbacks. No ideal localization technique is available; thus, the choice of preoperative assisted localization technique still depends on surgeons' preference and local availability of both specialists and instruments.
Topics: Consensus Development Conferences as Topic; Humans; Lung Neoplasms; Multiple Pulmonary Nodules; Practice Guidelines as Topic; Preoperative Care; Solitary Pulmonary Nodule; Thoracic Surgery, Video-Assisted; Tomography, X-Ray Computed
PubMed: 33004736
DOI: 10.4103/jcrt.JCRT_449_20