Aggregation of proteins containing expanded polyglutamine (polyQ) repeats is the cytopathologic hallmark of a group of dominantly inherited neurodegenerative diseases, including Huntington's disease (HD). Huntingtin (Htt), the disease protein of HD, forms amyloid-like fibrils by liquid-to-solid phase transition. Macroautophagy has been proposed to clear polyQ aggregates, but the efficiency of aggrephagy is limited. Here, we used cryo-electron tomography to visualize the interactions of autophagosomes with polyQ aggregates in cultured cells in situ. We found that an amorphous aggregate phase exists next to the radially organized polyQ fibrils. Autophagosomes preferentially engulfed this amorphous material, mediated by interactions between the autophagy receptor p62/SQSTM1 and the non-fibrillar aggregate surface. In contrast, amyloid fibrils excluded p62 and evaded clearance, resulting in trapping of autophagic structures. These results suggest that the limited efficiency of autophagy in clearing polyQ aggregates is due to the inability of autophagosomes to interact productively with the non-deformable, fibrillar disease aggregates.
Pubmed ID: 38759629 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal targets Mouse IgG (whole molecule)-Peroxidase antibody produced in goat
View all literature mentionsThis polyclonal targets Rabbit IgG (whole molecule)-Peroxidase antibody produced in goat
View all literature mentionsThis monoclonal targets polyQ
View all literature mentionsThis monoclonal targets Ubiquitin
View all literature mentionsThis polyclonal targets p62
View all literature mentionsThis monoclonal targets alpha-Tubulin
View all literature mentionsThis unknown targets LC3B
View all literature mentionsThis monoclonal targets MAP LC3beta (G-9)
View all literature mentionsThis monoclonal targets VCP antibody [5]
View all literature mentionsThis monoclonal targets Beta-Actin
View all literature mentionsThis monoclonal targets Myc Tag
View all literature mentionsUser interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.
View all literature mentionsSoftware toolbox for creating customized pediatric templates. It provides reference data based on imaging data from the NIH study of normal brain development. Using the general linear model, they statistically isolate the influence of external variables of interest on brain structure, allowing us to generate high-quality matched templates for any given group of subjects. The toolbox offers two options: # to create pediatric templates (T1) and tissue maps (GM, WM, and CSF) based on the objective 1 NIH data (n = 404), in the age range of 5-18 years, or # to assess a new reference population with regard to your variables of interest. Of note, this approach is generally applicable and in no way restricted to analyzing pediatric imaging data: for example, if you aim at investigating the effects of aging in elderly subjects, the toolbox will also allow you to create more appropriate reference (if your group is large enough to isolate such effects).
View all literature mentionsProgramming language for all operating systems that lets users work more quickly and integrate their systems more effectively. Often compared to Tcl, Perl, Ruby, Scheme or Java. Some of its key distinguishing features include very clear and readable syntax, strong introspection capabilities, intuitive object orientation, natural expression of procedural code, full modularity, exception-based error handling, high level dynamic data types, extensive standard libraries and third party modules for virtually every task, extensions and modules easily written in C, C (or Java for Python, or .NET languages for IronPython), and embeddable within applications as a scripting interface.
View all literature mentionsSoftware tool for visualizing, manipulating, and understanding data from tomography, microscopy, MRI and other imaging processes.Used to import and export options, to processes 3D image filtering and DTI based fiber tracking to visualization, volume and surface rendering, author tools for virtual reality navigation, video generation, and more.
View all literature mentionsA free, cross-platform set of image processing, modeling and display programs used for tomographic reconstruction and for 3D reconstruction of EM serial sections and optical sections. The package contains tools for assembling and aligning data within multiple types and sizes of image stacks, viewing 3-D data from any orientation, and modeling and display of the image files. IMOD 4.1.8 Is Now Available for Linux, Windows, and Mac OS X
View all literature mentionsSoftware tool for anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Used to describe the sample motion as a local deformation that varies smoothly throughout the exposure. A program running on Linux.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsSoftware tool for automated EM data acquisition. Used for efficient tilt series acquisition and interface for image capture, display, and storage and for control of some aspects of microscope function.
View all literature mentionsA set of fluorescence microscope image processing packages which perform image restoration, interactive analysis, and volume visualization of 2D and 3D multi channel microscopy images or time series. The restoration is based on different deconvolution algorithms, that permit the recovery of objects from images that are degraded by blurring and noise. Tutorials and documentation are available on the website.
View all literature mentionsSoftware that supports biological and biomedical researchers in interpreting protein quantification, interaction and post-translational modification data. Perseus contains a comprehensive portfolio of statistical tools for high-dimensional omics data analysis covering normalization, pattern recognition, time-series analysis, cross-omics comparisons and multiplehypothesis testing.
View all literature mentionsLeica DM6 B Upright Microscope includes the Leica DFC7000 T Camera and LAS X Software.
View all literature mentionsA quantitative proteomics software package for analyzing large-scale mass-spectrometric data sets. It is a set of algorithms that include peak detection and scoring of peptides, mass calibration, database searches for protein identification, protein quantification, and provides summary statistics.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsAn online resource which helps researchers manage and organize labs and experimental results by supplying molecular biology software tools for experimental design and data analysis. Benchling provides tools for functions such as primer design and colony counting as well as CRISPR guide design and automated Gibson and Golden Gate cloning. Users can take notes in line with data, link data across entries, keep files and data in one place, and manage and keep track of team progress. An enterprise version of Benchling is available for scientists working within an organization with additional administrative, compliance, and security protocols.
View all literature mentionsCell line Neuro2a-tNhtt-EGFP-150Q is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line Neuro2a-tNhtt-EGFP-60Q is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentions