Motor Clustering Enhances Kinesin-driven Vesicle Transport DOI Creative Commons
Rui Jiang,

Qingzhou Feng,

Daguan Nong

et al.

Published: Oct. 27, 2024

Abstract Intracellular vesicles are typically transported by a small number of kinesin and dynein motors. However, the slow microtubule binding rate kinesin-1 observed in vitro biophysical studies suggests that long-range transport may require high To address discrepancy motor requirements between vivo studies, we reconstituted motility 120-nm-diameter liposomes driven multiple GFP-labeled Consistent with predictions based on previous measurements, found long-distance requires We hypothesized this from observations arise differences organization tested whether clustering can enhance efficiency using DNA scaffold. Clustering just three motors improved liposome travel distances across wide range numbers. Our findings demonstrate that, independent number, arrangement vesicle regulates distance, suggesting explain disparity for transport. Significance Statement frequently long distances, despite having few By reconstituting motors, need copy numbers when randomly distributed surface. further show reduces required emphasizing its potential role enhancing efficiency. highlight significance regulating intracellular suggest clustering, such as scaffolding proteins or lipid domains, influences bidirectional outcomes.

Language: Английский

Cellular functions of actin- and microtubule-associated septins DOI Creative Commons
Elias T. Spiliotis,

Κωνσταντίνος Νάκος

Current Biology, Journal Year: 2021, Volume and Issue: 31(10), P. R651 - R666

Published: May 1, 2021

Language: Английский

Citations

118
The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases DOI Creative Commons

Minxue Xu,

Jie Ji, Dan-Dan Jin

et al.

Genes & Diseases, Journal Year: 2022, Volume and Issue: 10(5), P. 1894 - 1907

Published: April 22, 2022

Exosomes carry and transmit signaling molecules used for intercellular communication. The generation secretion of exosomes is a multistep interlocking process that allows simultaneous control multiple regulatory sites. Protein molecules, mainly RAB GTPases, cytoskeletal proteins soluble N-ethylmaleimide-sensitive fusion attachment protein receptor (SNARE), are specifically regulated in response to pathological conditions such as altered cellular microenvironment, stimulation by pathogenic factors, or gene mutation. This interferes with the smooth functioning endocytosis, translocation, degradation, docking processes, leading changes exosomes. Large numbers secreted disseminated flow body fluids absorbed recipient cells. By transmitting characteristic functional genetic information produced under disease conditions, can change physiological state cells their microenvironment. turn, affects occurrence development disease. Therefore, this review will discuss mechanism which exosome following formation mature secretory multivesicular bodies (MVBs). overall aim find ways eliminate disease-derived at source, thereby providing an important new basis clinical treatment

Language: Английский

Citations

107
Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology DOI
Carmine Settembre, Rushika M. Perera

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 223 - 245

Published: Nov. 24, 2023

Language: Английский

Citations

95
The Structural Biology of Septins and Their Filaments: An Update DOI Creative Commons
Ítalo A. Cavini, Diego A. Leonardo, Higor Vinícius Dias Rosa

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Nov. 19, 2021

In order to fully understand any complex biochemical system from a mechanistic point of view, it is necessary have access the three-dimensional structures molecular components involved. Septins and their oligomers, filaments higher-order complexes are no exception. Indeed, spontaneous recruitment different septin monomers specific positions along filament represents fascinating example subtle recognition. Over last few years, amount structural information available about these important cytoskeletal proteins has increased dramatically. This allowed for more detailed description individual domains interfaces formed between them, which basis stabilizing such as hexamers, octamers filaments. The flexibility plasticity also begun be understood. Furthermore, recently, light been shed on how may bundle into by formation antiparallel coiled coils involving C-terminal domains. Nevertheless, even with advances, there still some way go before we structure dynamics assemblies related physiological roles, including interactions biological membranes other components. this review, aim bring together various strands evidence currently coherent picture. Although would an exaggeration say that complete, recent progress seems suggest headway being made in direction.

Language: Английский

Citations

62
RUFY3 and RUFY4 are ARL8 effectors that promote coupling of endolysosomes to dynein-dynactin DOI Creative Commons
Tal Keren‐Kaplan, Amra Sarić, Saikat Ghosh

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 21, 2022

The small GTPase ARL8 associates with endolysosomes, leading to the recruitment of several effectors that couple endolysosomes kinesins for anterograde transport along microtubules, and tethering factors eventual fusion other organelles. Herein we report identification RUN- FYVE-domain-containing proteins RUFY3 RUFY4 as promote coupling dynein-dynactin retrograde microtubules. Using various methodologies, find interact both GTP-bound dynein-dynactin. In addition, show concentration in juxtanuclear area non-neuronal cells, drive redistribution from axon soma hippocampal neurons. function contributes upon cytosol alkalinization. These studies thus identify ARL8-dependent, adaptors or regulators, highlight role control endolysosome transport.

Language: Английский

Citations

59
RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning DOI Creative Commons
Gaurav Kumar, Prateek Chawla, Neha Dhiman

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 21, 2022

Abstract The bidirectional movement of lysosomes on microtubule tracks regulates their whole-cell spatial arrangement. Arl8b, a small GTP-binding (G) protein, promotes lysosome anterograde trafficking mediated by kinesin-1. Herein, we report an Arl8b effector, RUFY3, which the retrograde transport lysosomes. We show that RUFY3 interacts with JIP4-dynein-dynactin complex and facilitates association motor complex. Accordingly, knockdown disrupts positioning Arl8b-positive endosomes reduces colocalization Rab7-marked late endosomal compartments. Moreover, find nutrient-dependent distribution, although autophagosome-lysosome fusion autophagic cargo degradation are not impaired upon depletion. Interestingly, size is significantly reduced in depleted cells, could be rescued inhibition reformation regulatory factor PIKFYVE. These findings suggest model perinuclear cloud arrangement both these proteolytic

Language: Английский

Citations

56
N4‐Acetylcytidine Drives Glycolysis Addiction in Gastric Cancer via NAT10/SEPT9/HIF‐1α Positive Feedback Loop DOI Creative Commons
Qingbin Yang,

Xuetao Lei,

Jiayong He

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(23)

Published: June 16, 2023

Anti-angiogenic therapy has long been considered a promising strategy for solid cancers. Intrinsic resistance to hypoxia is major cause the failure of anti-angiogenic therapy, but underlying mechanism remains unclear. Here, it revealed that N4-acetylcytidine (ac4C), newly identified mRNA modification, enhances tolerance in gastric cancer (GC) cells by promoting glycolysis addiction. Specifically, acetyltransferase NAT10 transcription regulated HIF-1α, key factor cellular response hypoxia. Further, acRIP-sequencing, Ribosome profiling sequencing, RNA-sequencing, and functional studies confirm turn activates HIF-1 pathway subsequent glucose metabolism reprogramming mediating SEPT9 ac4C modification. The formation NAT10/SEPT9/HIF-1α positive feedback loop leads excessive activation induces Combined anti-angiogenesis inhibition attenuate inhibit tumor progression vivo. This study highlights critical roles regulation addiction proposes overcome combining apatinib with inhibition.

Language: Английский

Citations

35
Septins as membrane influencers: direct play or in association with other cytoskeleton partners DOI Creative Commons
Béatrice Benoit, Christian Poüs,

Anita Baillet

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 17, 2023

The cytoskeleton comprises three polymerizing structures that have been studied for a long time, actin microfilaments, microtubules and intermediate filaments, plus more recently investigated dynamic assemblies like septins or the endocytic-sorting complex required transport (ESCRT) complex. These filament-forming proteins control several cell functions through crosstalks with each other membranes. In this review, we report recent works address how bind to membranes, influence their shaping, organization, properties functions, either by binding them directly indirectly elements.

Language: Английский

Citations

24
DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy DOI Creative Commons
Rahul Kumar, Maleeha Khan,

Vincent Francis

et al.

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

Published: Jan. 31, 2024

Lysosomes help maintain cellular proteostasis, and defects in lysosomal positioning function can cause disease, including neurodegenerative disorders. The spatiotemporal distribution of lysosomes is regulated by small GTPases Rabs, which are activated guanine nucleotide exchange factors (GEFs). DENN domain proteins the largest family Rab GEFs. Using a cell-based assay, we screened DENND6A, member protein against all known Rabs identified it as potential GEF for 20 Rab34. Here, demonstrate that DENND6A activates Rab34, recruits RILP/dynein complex to lysosomes, promoting lysosome retrograde transport. Further, identify an effector Arl8b, major regulatory GTPase on lysosomes. We Arl8b peripheral activate Rab34 initiate transport, regulating nutrient-dependent juxtanuclear repositioning. Loss impairs autophagic flux. Our findings support model whereby Arl8b/DENND6A/Rab34-dependent trafficking controls autophagy.

Language: Английский

Citations

7
Lysosomal positioning diseases: beyond substrate storage DOI Creative Commons
Gianluca Scerra, Valeria De Pasquale, Melania Scarcella

et al.

Open Biology, Journal Year: 2022, Volume and Issue: 12(10)

Published: Oct. 1, 2022

Lysosomal storage diseases (LSDs) comprise a group of inherited monogenic disorders characterized by lysosomal dysfunctions due to undegraded substrate accumulation. They are caused deficiency in specific hydrolases involved cellular catabolism, or non-enzymatic proteins essential for normal functions. In LSDs, the lack degradation accumulated and its impairs lysosome functions resulting perturbation homeostasis and, turn, damage multiple organ systems. A substantial number studies on pathogenesis LSDs has highlighted how accumulation substrates is only first event cascade processes including secondary metabolites impairment trafficking, cell signalling, autophagic flux, mitochondria functionality calcium homeostasis, that significantly contribute onset progression these diseases. Emerging biology have described fundamental roles organelles variety physiological pathological conditions beyond their canonical activity waste clearance. Here, we discuss recent advances knowledge molecular mechanisms linking positioning trafficking LSDs.

Language: Английский

Citations

27