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

Cytoskeleton and Associated Proteins: Pleiotropic JNK Substrates and Regulators DOI Open Access
Béatrice Benoit,

Anita Baillet,

Christian Poüs

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(16), P. 8375 - 8375

Published: Aug. 4, 2021

This review extensively reports data from the literature concerning complex relationships between stress-induced c-Jun N-terminal kinases (JNKs) and four main cytoskeleton elements, which are actin filaments, microtubules, intermediate septins. To a lesser extent, we also focused on two membrane-associated cytoskeletons spectrin ESCRT-III. We gather mechanisms controlling cytoskeleton-associated JNK activation known cytoskeleton-related substrates directly phosphorylated by JNK. point out specific locations of upstream regulators at cytoskeletal components. finally compile available techniques tools that could allow better characterization interplay different types filaments upon JNK-mediated stress during development. overview may bring new important information for applied medical research.

Language: Английский

Citations

32
Endosomal sorting sorted – motors, adaptors and lessons fromin vitroand cellular studies DOI Open Access
Gregory Redpath, Vaishnavi Ananthanarayanan

Journal of Cell Science, Journal Year: 2023, Volume and Issue: 136(5)

Published: March 1, 2023

ABSTRACT Motor proteins are key players in exerting spatiotemporal control over the intracellular location of membrane-bound compartments, including endosomes containing cargo. In this Review, we focus on how motors and their cargo adaptors regulate positioning cargoes from earliest stages endocytosis through two main itineraries: (1) degradation at lysosome or (2) recycling back to plasma membrane. vitro cellular (in vivo) studies transport thus far have typically focussed independently either motor adaptors, membrane trafficking. Here, will discuss recent highlight what is known about regulation endosomal vesicle by adaptors. We also emphasise that often performed different scales, single molecules whole organelles, with aim provide a perspective unified principles motor-driven trafficking living cells can be learned these differing scales.

Language: Английский

Citations

11
The axonal endolysosomal and autophagic systems DOI Creative Commons
Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke

et al.

Journal of Neurochemistry, Journal Year: 2020, Volume and Issue: 158(3), P. 589 - 602

Published: Dec. 29, 2020

Neurons, because of their elaborate morphology and the long distances between distal axons soma as well longevity, pose special challenges to autophagy endolysosomal system, two main degradative routes for turnover defective proteins organelles. Autophagosomes sequester cytoplasmic or organellar cargos by engulfing them into lumen before fusion with lysosomes enriched in neuronal somata participate retrograde signaling soma. Endosomes are mainly involved sorting, recycling, lysosomal internalized membrane-bound macromolecules maintain axonal membrane homeostasis. Lysosomes multiple shades lysosome-related organelles also serve non-degradative roles, example, nutrient synapse formation. Recent years have begun shed light on distinctive organization systems neurons, particular roles axons. We review here our current understanding localization, distribution, growing list functions these axon health disease outline perspectives future research.

Language: Английский

Citations

30
Spatial regulation of microtubule-dependent transport by septin GTPases DOI
Elias T. Spiliotis,

Ilona A. Kesisova

Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 31(12), P. 979 - 993

Published: July 9, 2021

Language: Английский

Citations

26
Oxidative stress‐induced phosphorylation of JIP4 regulates lysosomal positioning in coordination with TRPML1 and ALG2 DOI Creative Commons
Yukiko Sasazawa,

Sanae Souma,

Norihiko Furuya

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(22)

Published: Oct. 11, 2022

Abstract Retrograde transport of lysosomes is recognised as a critical autophagy regulator. Here, we found that acrolein, an aldehyde significantly elevated in Parkinson's disease patient serum, enhances by promoting lysosomal clustering around the microtubule organising centre via newly identified JIP4‐TRPML1‐ALG2 pathway. Phosphorylation JIP4 at T217 CaMK2G response to Ca 2+ fluxes tightly regulated this system. Increased vulnerability KO cells acrolein indicated and subsequent activation served defence mechanisms against cytotoxicity itself. Furthermore, pathway was also activated H 2 O , indicating system acts broad mechanism oxidative stress response. Conversely, starvation‐induced retrograde involved both TMEM55B‐JIP4 TRPML1‐ALG2 pathways absence phosphorylation. Therefore, phosphorylation status switch controls signalling lysosoma l distribution depending on type autophagy‐inducing signal.

Language: Английский

Citations

16
Right place, right time - Spatial guidance of neuronal morphogenesis by septin GTPases DOI Creative Commons
Megan R. Radler, Elias T. Spiliotis

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 75, P. 102557 - 102557

Published: May 21, 2022

Language: Английский

Citations

13
Neuronal-specific septin-3 binds Atg8/LC3B, accumulates and localizes to autophagosomes during induced autophagy DOI Creative Commons
Vilmos Tóth,

Henrietta Vadászi,

Lilla Ravasz

et al.

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(9)

Published: Aug. 6, 2022

In synapses that show signs of local apoptosis and mitochondrial stress undergo neuro-immunological synapse pruning, an increase in the levels presynaptic protein, neuronal-specific septin-3 can be observed. Septin-3 is a member septin GTPase family with ability to form multimers contribute cytoskeleton. However, function remains elusive. Here, we provide evidence capable binding most-studied autophagy protein Atg8 homolog microtubule-associated 1 light chain 3B (LC3B), besides another homolog, GABA receptor-associated protein-like 2 (GABARAPL2). Moreover, demonstrate colocalization LC3B increases upon chemical induction primary neuronal cells. accumulated neurons enhancement or blockade, similar proteins. Using electron microscopy, also localizes positive membranes found at mitochondria. results early mitophagy marker PTEN-induced kinase (PINK1) do not support mitochondria related. We conclude correlates synaptic/neuronal autophagy, binds autophagic enhanced induction. Based on our results, elevated might indicate impeded neurons.

Language: Английский

Citations

13
Septins as key players in spermatogenesis, fertilisation and pre-implantation embryogenic cytoplasmic dynamics DOI Creative Commons

Hana Al-Ali,

Amna Baig,

Rayyah R. Alkhanjari

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Oct. 28, 2024

Septins are a family of cytokinesis-related proteins involved in regulating cytoskeletal design, cell morphology, and tissue morphogenesis. Apart from cytokinesis, as fourth component cytoskeleton, septins aid forming scaffolds, vesicle sorting membrane stability. They also known to be the regulation intracellular calcium (Ca2+) via STIM/Orai complex. Infertility affects ~ 15% couples globally, while male infertility 7% men. Global pregnancy live birth rates following fertility treatment remain relatively low, there has been an observable decline parameters over past 60 years. Low success can attributed poor embryonic development, sperm fertilisation defects. While studies few years have provided evidence for role related processes, functional its complexes cellular processes such oocyte activation, fertilization, maturation not completely understood. This review summarizes available knowledge on spermatogenesis activation Ca2+ regulation, dynamics throughout pre-implantation development. We aim identify currently less mechanisms by which regulate these immensely important with view identifying areas investigation that would benefit our understanding reproductive biology, but provide potential avenues improve current methods treatment.

Language: Английский

Citations

2
Dynamics and distribution of endosomes and lysosomes in dendrites DOI Creative Commons
Chan Choo Yap, Ashley J Mason, Bettina Winckler

et al.

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 74, P. 102537 - 102537

Published: April 8, 2022

Language: Английский

Citations

9
Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities DOI Creative Commons
Ayana Suber, Md Noor A. Alam,

Κωνσταντίνος Νάκος

et al.

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(9), P. 105084 - 105084

Published: July 24, 2023

Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a code. The regulatory principles of this code how it orchestrates the motility kinesin dynein motors are largely unknown. Septins large family GTP-binding proteins, assemble into complexes that associate with microtubules. Using single-molecule in vitro assays, we tested SEPT2/6/7, SEPT2/6/7/9, SEPT5/7/11 affect motilities constitutively active kinesins KIF5C KIF1A dynein-dynactin-bicaudal D (DDB) motor complex. We found SEPT2/6/7 potent inhibitor DDB KIF5C, preventing mainly their association also inhibits obstructing stepping along On SEPT2/6/7/9-coated microtubules, inhibition dampened SEPT9, alone enhances KIF1A, showing individual septin subunits determine properties complexes. Strikingly, differs from permitting immobilizing to microtubule lattice. In hippocampal neurons, filamentous SEPT5 colocalizes somatodendritic microtubules underlie Golgi membranes lack SEPT6. Depletion disrupts morphology polarization ribbons shaft somato-proximal dendrites, consistent tethering SEPT5/7/11. Collectively, these results suggest have differential specificities regulation positioning motors. posit septins an integral part microtubule-based spatially controls traffic.

Language: Английский

Citations

5