SEPT9_i1 and Septin Dynamics in Oncogenesis and Cancer Treatment DOI Creative Commons
Piotr Jędrzejczak, Kamil Saramowicz,

Justyna Kuś

и другие.

Biomolecules, Год журнала: 2024, Номер 14(9), С. 1194 - 1194

Опубликована: Сен. 22, 2024

Despite significant advancements in the field of oncology, cancers still pose one greatest challenges modern healthcare. Given cytoskeleton’s pivotal role regulating mechanisms critical to cancer development, further studies cytoskeletal elements could yield new practical applications. Septins represent a group relatively well-conserved GTP-binding proteins that constitute fourth component cytoskeleton. Septin 9 (SEPT9) has been linked diverse spectrum malignancies and appears be most notable septin member category. SEPT9 constitutes biomarker colorectal (CRC) positively correlated with high clinical stage breast cancer, cervical head neck squamous cell carcinoma. SEPT9_i1 represents extensively studied isoform SEPT9, which substantially contributes carcinogenesis, metastasis, treatment resistance. Nevertheless, mechanistic basis oncogenicity remains fully elucidated. In this review, we highlight SEPT9’s SEPT9_i1’s structures interactions Hypoxia Inducible Factor α (HIF-1 α) C-Jun N-Terminal Kinase (JNK), as well discuss contribution aneuploidy, invasiveness, taxane resistance—key phenomena progression malignancies. Finally, emphasize forchlorfenuron other inhibitors potential chemotherapeutics migrastatics.

Язык: Английский

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

и другие.

Open Biology, Год журнала: 2022, Номер 12(10)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

28
The axonal endolysosomal and autophagic systems DOI Creative Commons
Marijn Kuijpers, Domenico Azarnia Tehran, Volker Haucke

и другие.

Journal of Neurochemistry, Год журнала: 2020, Номер 158(3), С. 589 - 602

Опубликована: Дек. 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.

Язык: Английский

Процитировано

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

Ilona A. Kesisova

Trends in Cell Biology, Год журнала: 2021, Номер 31(12), С. 979 - 993

Опубликована: Июль 9, 2021

Язык: Английский

Процитировано

26
Endosomal sorting sorted – motors, adaptors and lessons fromin vitroand cellular studies DOI Open Access
Gregory Redpath, Vaishnavi Ananthanarayanan

Journal of Cell Science, Год журнала: 2023, Номер 136(5)

Опубликована: Март 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.

Язык: Английский

Процитировано

11
Oxidative stress‐induced phosphorylation of JIP4 regulates lysosomal positioning in coordination with TRPML1 and ALG2 DOI Creative Commons
Yukiko Sasazawa,

Sanae Souma,

Norihiko Furuya

и другие.

The EMBO Journal, Год журнала: 2022, Номер 41(22)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

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, Год журнала: 2022, Номер 75, С. 102557 - 102557

Опубликована: Май 21, 2022

Язык: Английский

Процитировано

14
Neuronal-specific septin-3 binds Atg8/LC3B, accumulates and localizes to autophagosomes during induced autophagy DOI Creative Commons
Vilmos Tóth,

Henrietta Vadászi,

Lilla Ravasz

и другие.

Cellular and Molecular Life Sciences, Год журнала: 2022, Номер 79(9)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

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

и другие.

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Окт. 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.

Язык: Английский

Процитировано

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

и другие.

Current Opinion in Neurobiology, Год журнала: 2022, Номер 74, С. 102537 - 102537

Опубликована: Апрель 8, 2022

Язык: Английский

Процитировано

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

Κωνσταντίνος Νάκος

и другие.

Journal of Biological Chemistry, Год журнала: 2023, Номер 299(9), С. 105084 - 105084

Опубликована: Июль 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.

Язык: Английский

Процитировано

5