Phase separation of microtubule-binding proteins – implications for neuronal function and disease DOI
Daisy Duan, Anthony J. Koleske

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(24)

Published: Dec. 13, 2024

ABSTRACT Protein liquid–liquid phase separation (LLPS) is driven by intrinsically disordered regions and multivalent binding domains, both of which are common features diverse microtubule (MT) regulators. Many in vitro studies have dissected the mechanisms MT-binding proteins (MBPs) regulate MT nucleation, stabilization dynamics, investigated whether LLPS plays a role these processes. However, more recent vivo focused on how MBP affects biological functions throughout neuronal development. Dysregulation can lead to formation aggregates – an underlying feature many neurodegenerative diseases such as tau neurofibrillary tangles present Alzheimer's disease. In this Review, we highlight progress towards understanding regulation dynamics through lens MBPs associated cytoskeletal regulators, from studies. We also discuss regulates development maintains homeostasis mature neurons.

Language: Английский

Synthetic nucleic-acid droplets: a bioprogramming platform for designer microliquids DOI Creative Commons
Hirotake Udono,

Tomoya Maruyama,

Nathan N. Evangelista

et al.

Polymer Journal, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

Language: Английский

Citations

0
The potential role of liquid–liquid phase separation in the cellular fate of the compartments for unconventional protein secretion DOI
Luís F.S. Mendes,

Carolina O. Gimenes,

Marília D. O. da Silva

et al.

Protein Science, Journal Year: 2024, Volume and Issue: 33(7)

Published: June 26, 2024

Abstract Eukaryotic cells have developed intricate mechanisms for biomolecule transport, particularly in stressful conditions. This interdisciplinary study delves into unconventional protein secretion (UPS) pathways activated during starvation, facilitating the export of proteins bypassing most components classical secretory machinery. Specifically, we focus on underexplored GRASP's role UPS, biogenesis and cargo recruitment vesicular‐like compartment UPS. Our results show that liquid–liquid phase separation (LLPS) plays a key coacervation Grh1, GRASP yeast homologue, under starvation‐like association seems precursor to Compartment Unconventional Protein Secretion (CUPS) biogenesis. Grh1's self‐association is regulated by electrostatic, hydrophobic, hydrogen‐bonding interactions. Importantly, our demonstrates phase‐separated states Grh1 can recruit UPS situations. Additionally, explore how coacervate liquid‐to‐solid transition could impact cells' ability return normal post‐stress states. findings offer insights intracellular dynamics cell adaptive responses stress.

Language: Английский

Citations

2
Distinguishing Protein Corona from Nanoparticle Aggregate Formation in Complex Biological Media Using X-ray Photon Correlation Spectroscopy DOI Creative Commons
Caroline E.P. Silva, Agustı́n S. Picco, Flávia Elisa Galdino

et al.

Nano Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

In biological systems, nanoparticles interact with biomolecules, which may undergo protein corona formation that can result in noncontrolled aggregation. Therefore, comprehending the behavior and evolution of presence fluids is paramount nanomedicine. However, traditional lab-based colloid methods characterize diluted suspensions low-complexity media, hinders in-depth studies complex environments. Here, we apply X-ray photon correlation spectroscopy (XPCS) to investigate silica (SiO

Language: Английский

Citations

2
Exploring liquid-liquid phase separation in the organisation of Golgi matrix proteins DOI
Luís F.S. Mendes, Carolina Boschi Gimenes,

Kevin F. Simões

et al.

Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Journal Year: 2024, Volume and Issue: 1872(5), P. 141029 - 141029

Published: June 24, 2024

Language: Английский

Citations

1
(Dys)functional insights into nucleic acids and RNA-binding proteins modulation of the prion protein and α-synuclein phase separation DOI
Yraima Cordeiro, Maria Heloisa O. Freire,

Adalgisa Felippe Wiecikowski

et al.

Biophysical Reviews, Journal Year: 2023, Volume and Issue: 15(4), P. 577 - 589

Published: June 6, 2023

Language: Английский

Citations

2
Chaperone-mediated heterotypic phase separation prevents the amyloid formation of the pathological Y145Stop variant of the prion protein DOI

Lisha Arora,

Dipankar Bhowmik,

Snehasis Sarkar

et al.

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

Published: Sept. 8, 2024

Abstract Biomolecular condensates formed via phase separation of proteins and nucleic acids are crucial for the spatiotemporal regulation a diverse array essential cellular functions maintenance homeostasis. However, aberrant liquid-to-solid transitions such associated with several fatal human diseases. Such dynamic membraneless compartments can contain range molecular chaperones that regulate behavior involved in formation these biological condensates. Here, we show heat shock protein 40 (Hsp40), Ydj1, exhibits holdase activity by potentiating disease-associated stop codon mutant prion (Y145Stop) either recruitment into Y145Stop or Y145Stop-Ydj1 two-component heterotypic prevents conformational conversion amyloid fibrils. Utilizing site-directed mutagenesis, multicolor fluorescence imaging, single-droplet steady-state picosecond time-resolved anisotropy, recovery after photobleaching, correlation spectroscopy, delineate complex network interactions govern Ydj1. We also properties further be tuned RNA promotes multicomponent multiphasic protein-RNA Our vibrational Raman spectroscopy results conjunction atomic force microscopy imaging reveal Ydj1 effectively redirects self-assembly towards dynamically-arrested non-amyloidogenic pathway, preventing typical findings underscore importance chaperone-mediated regulating wide deadly neurodegenerative

Language: Английский

Citations

0
Intermolecular Energy Migration via HomoFRET Captures the Modulation in the Material Property of Phase-Separated Biomolecular Condensates DOI Open Access

Ashish Joshi,

Anuja Walimbe,

Snehasis Sarkar

et al.

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

Published: Feb. 12, 2024

Abstract Biomolecular condensation via phase separation of proteins and nucleic acids has emerged as a crucial mechanism underlying the spatiotemporal organization cellular components into functional membraneless organelles. However, aberrant maturation these dynamic, liquid-like assemblies irreversible gel-like or solid-like aggregates is associated with wide range fatal neurodegenerative diseases. New tools are essential to dissect changes in internal material properties biomolecular condensates that often modulated by factors involving sequence composition, truncations, mutations, post-translational modifications, stoichiometry other biomolecules. Here, we employ homo-Förster Resonance Energy Transfer (homoFRET) proximity ruler study intermolecular energy migration illuminates molecular packing nanometric length-scale within condensates. We used homoFRET efficiency, measured loss fluorescence anisotropy due rapid depolarization, readout giving rise Using single-droplet imaging, recorded spatially-resolved efficiencies formed fluorescent protein-tagged Fused Sarcoma (FUS). By performing picosecond time-resolved measurements, were able discern various events dense network polypeptide chains FUS Our studies also captured modulation RNA, ATP, modification. Additionally, utilized mammalian cell lines stably expressing nuclear oxidative stress-induced stress granule formation cytoplasm. demonstrate methodology offers potent tool for studying intracellular transitions physiology disease.

Language: Английский

Citations

0
Intermolecular energy migration via homoFRET captures the modulation in the material property of phase-separated biomolecular condensates DOI Creative Commons

Ashish Joshi,

Anuja Walimbe,

Snehasis Sarkar

et al.

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

Published: Oct. 25, 2024

Physical properties of biomolecular condensates formed via phase separation proteins and nucleic acids are associated with cell physiology disease. Condensate can be regulated by several cellular factors including post-translational modifications. Here, we introduce an application intermolecular energy migration homo-FRET (Förster resonance transfer), a nanometric proximity ruler, to study the modulation in short- long-range protein-protein interactions leading changes physical fluorescently-tagged FUS (Fused Sarcoma) that is formation cytoplasmic nuclear membraneless organelles. We show homoFRET captures modulations condensate RNA, ATP, arginine methylation. also extend methodology in-situ stress granules mammalian cells. Our studies highlight broad applicability as potent generic tool for studying intracellular transitions involved function

Language: Английский

Citations

0
Phase separation of microtubule-binding proteins – implications for neuronal function and disease DOI
Daisy Duan, Anthony J. Koleske

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(24)

Published: Dec. 13, 2024

ABSTRACT Protein liquid–liquid phase separation (LLPS) is driven by intrinsically disordered regions and multivalent binding domains, both of which are common features diverse microtubule (MT) regulators. Many in vitro studies have dissected the mechanisms MT-binding proteins (MBPs) regulate MT nucleation, stabilization dynamics, investigated whether LLPS plays a role these processes. However, more recent vivo focused on how MBP affects biological functions throughout neuronal development. Dysregulation can lead to formation aggregates – an underlying feature many neurodegenerative diseases such as tau neurofibrillary tangles present Alzheimer's disease. In this Review, we highlight progress towards understanding regulation dynamics through lens MBPs associated cytoskeletal regulators, from studies. We also discuss regulates development maintains homeostasis mature neurons.

Language: Английский

Citations

0