Biophysical Modeling of Synaptic Plasticity DOI
Christopher T. Lee, Miriam Bell, Mayte Bonilla-Quintana

et al.

Annual Review of Biophysics, Journal Year: 2024, Volume and Issue: 53(1), P. 397 - 426

Published: Feb. 21, 2024

Dendritic spines are small, bulbous compartments that function as postsynaptic sites and undergo intense biochemical biophysical activity. The role of the myriad signaling pathways implicated in synaptic plasticity is well studied. A recent abundance quantitative experimental data has made events associated with amenable to modeling. Spines also fascinating computational units because spine geometry, signal transduction, mechanics work a complex feedback loop tune plasticity. In this sense, ideas from modeling cell motility can inspire us develop multiscale approaches for predictive article, we review key steps specific focus on impact geometry signaling, cytoskeleton rearrangement, membrane mechanics. We summarize main observations highlight how theory computation aid our understanding these processes.

Language: Английский

Bringing Structure to Cell Biology with Cryo-Electron Tomography DOI Creative Commons
Lindsey N. Young, Elizabeth Villa

Annual Review of Biophysics, Journal Year: 2023, Volume and Issue: 52(1), P. 573 - 595

Published: May 9, 2023

Recent advances in cryo-electron microscopy have marked only the beginning of potential this technique. To bring structure into cell biology, modality tomography has fast developed a bona fide situ structural biology technique where structures are determined their native environment, cell. Nearly every step cryo-focused ion beam-assisted electron (cryo-FIB-ET) workflow been improved upon past decade, since first windows were carved cells, unveiling macromolecular networks near-native conditions. By bridging and cryo-FIB-ET is advancing our understanding structure–function relationships environment becoming tool for discovering new biology.

Language: Английский

Citations

80
Making the connection: How membrane contact sites have changed our view of organelle biology DOI Creative Commons
Gia K. Voeltz, Eric M. Sawyer, György Hajnóczky

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 257 - 270

Published: Jan. 1, 2024

The view of organelles and how they operate together has changed dramatically over the last two decades. textbook was that operated largely independently were connected by vesicular trafficking diffusion signals through cytoplasm. We now know all make functional close contacts with one another, often called membrane contact sites. study these sites moved to center stage in cell biology as it become clear play critical roles healthy developing cells during stress disease states. Contact have important intracellular signaling, lipid metabolism, motor-protein-mediated dynamics, organelle division, biogenesis. Here, we summarize major conceptual changes occurred come appreciate integrate activities organelles.

Language: Английский

Citations

60
MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography DOI Creative Commons
Lorenz Lamm,

Simon Zufferey,

Ricardo D. Righetto

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 5, 2024

A bstract MemBrain v2 is a deep learning-enabled program aimed at the efficient analysis of membranes in cryo-electron tomography (cryo-ET). The final release will comprise three main modules: 1) MemBrain-seg, which provides automated membrane segmentation, 2) MemBrain-pick, picking particles along segmented membranes, and 3) MemBrain-stats, quantitative statistics particle distributions morphometrics. This initial version manuscript focused on beta combines iterative training with diverse data specialized Fourier-based augmentations. These augmentations are specifically designed to enhance tool’s adaptability variety tomographic address common challenges cryo-ET analysis. key feature MemBrain-seg implementation Surface-Dice loss function, improves network’s focus connectivity allows for effective incorporation manual annotations from different sources. function beneficial handling variability inherent structures annotations. Our ongoing collaboration community plays an important role continually improving wide array data. collaborative approach ensures that remains attuned field’s needs, enhancing its robustness generalizability across types current available https://github.com/teamtomo/membrain-seg , predecessor MemBrain-pick (also called v1) deposited https://github.com/CellArchLab/MemBrain . preprint be updated concomitantly code until integrated modules complete.

Language: Английский

Citations

59
Bridging structural and cell biology with cryo-electron microscopy DOI
Eva Nogales, Julia Mahamid

Nature, Journal Year: 2024, Volume and Issue: 628(8006), P. 47 - 56

Published: April 3, 2024

Language: Английский

Citations

58
RBG Motif Bridge-Like Lipid Transport Proteins: Structure, Functions, and Open Questions DOI Creative Commons
Michael G. Hanna, Andrés Guillén-Samander, Pietro De Camilli

et al.

Annual Review of Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 39(1), P. 409 - 434

Published: July 5, 2023

The life of eukaryotic cells requires the transport lipids between membranes, which are separated by aqueous environment cytosol. Vesicle-mediated traffic along secretory and endocytic pathways lipid transfer proteins (LTPs) cooperate in this transport. Until recently, known LTPs were shown to carry one or a few at time thought mediate shuttle-like mechanisms. Over last years, new family has been discovered that is defined repeating β-groove (RBG) rod-like structure with hydrophobic channel running their entire length. This localization these membrane contact sites suggest bridge-like mechanism Mutations some result neurodegenerative developmental disorders. Here we review properties well-established putative physiological roles proteins, highlight many questions remain open about functions.

Language: Английский

Citations

55
Integrating cellular electron microscopy with multimodal data to explore biology across space and time DOI Creative Commons
Caitlyn L McCafferty, Sven Klumpe, Rommie E. Amaro

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 563 - 584

Published: Feb. 1, 2024

Biology spans a continuum of length and time scales. Individual experimental methods only glimpse discrete pieces this spectrum but can be combined to construct more holistic view. In Review, we detail the latest advancements in volume electron microscopy (vEM) cryo-electron tomography (cryo-ET), which together visualize biological complexity across scales from organization cells large tissues molecular details inside native cellular environments. addition, discuss emerging methodologies for integrating three-dimensional (3DEM) imaging with multimodal data, including fluorescence microscopy, mass spectrometry, single-particle analysis, AI-based structure prediction. This multifaceted approach fills gaps continuum, providing functional context, spatial organization, identity, interactions. We conclude perspective on incorporating diverse data into computational simulations that further bridge extend while dimension time.

Language: Английский

Citations

45
High-confidence 3D template matching for cryo-electron tomography DOI Creative Commons
Sergio Cruz-León, Tomáš Majtner, Patrick C. Hoffmann

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 11, 2024

Abstract Visual proteomics attempts to build atlases of the molecular content cells but automated annotation cryo electron tomograms remains challenging. Template matching (TM) and methods based on machine learning detect structural signatures macromolecules. However, their applicability limited in terms both abundance size targets. Here we show that performance TM is greatly improved by using template-specific search parameter optimization including higher-resolution information. We establish a pipeline with systematically tuned parameters for automated, objective comprehensive identification structures confidence 10 100-fold above noise level. demonstrate high-fidelity high-confidence localizations nuclear pore complexes, vaults, ribosomes, proteasomes, fatty acid synthases, lipid membranes microtubules, individual subunits inside crowded eukaryotic cells. provide software tools generic implementation our method broadly applicable towards realizing visual proteomics.

Language: Английский

Citations

34
The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria DOI Creative Commons
Christian Koch, Svenja Lenhard, Markus Räschle

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(4), P. 2071 - 2096

Published: April 2, 2024

Most mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria in a post-translational reaction. Mitochondrial precursor which use the ER-SURF pathway employ surface of endoplasmic reticulum (ER) as an important sorting platform. How they reach import machinery from ER is not known. Here we show that contact sites play crucial role ER-to-mitochondria transfer proteins. The encounter structure (ERMES) Tom70, together with Djp1 Lam6, part two parallel partially redundant delivery routes. When prevented by loss these sites, many precursors inner membrane left stranded membrane, resulting dysfunction. Our observations support active protein biogenesis.

Language: Английский

Citations

21
In situ architecture of the human prohibitin complex DOI Creative Commons

F. de Lange,

Michael Ratz,

Jan-Niklas Dohrke

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Abstract Prohibitins are a highly conserved family of proteins that have been implicated in variety functions including mitochondrial stress signalling and housekeeping, cell cycle progression, apoptosis, lifespan regulation many others. The human prohibitins prohibitin 1 2 proposed to act as scaffolds within the inner membrane, but their molecular organization has remained elusive. Here we determined complex membrane using an integrative structural biology approach combining quantitative western blotting, cryo-electron tomography, subtomogram averaging modelling. bell-shaped structure consists 11 alternating molecules. This study reveals average about 43 complexes per crista, covering 1–3% crista area. These findings provide basis for understanding functional contributions integrity spatial membrane.

Language: Английский

Citations

2
Genetically encoded multimeric tags for subcellular protein localization in cryo-EM DOI Creative Commons
Herman K.H. Fung, Yuki Hayashi, Veijo T. Salo

et al.

Nature Methods, Journal Year: 2023, Volume and Issue: 20(12), P. 1900 - 1908

Published: Nov. 6, 2023

Abstract Cryo-electron tomography (cryo-ET) allows for label-free high-resolution imaging of macromolecular assemblies in their native cellular context. However, the localization macromolecules interest tomographic volumes can be challenging. Here we present a ligand-inducible labeling strategy intracellular proteins based on fluorescent, 25-nm-sized, genetically encoded multimeric particles (GEMs). The exhibit recognizable structural signatures, enabling automated detection cryo-ET data by convolutional neural networks. coupling GEMs to green fluorescent protein-tagged is triggered addition small-molecule ligand, allowing time-controlled minimize disturbance protein function. We demonstrate applicability subcellular-level endogenous and overexpressed across different organelles human cells using cryo-correlative fluorescence imaging. describe means quantifying specificity efficiency, systematic optimization rare abundant targets, with emphasis assessing potential effects

Language: Английский

Citations

26